Skin discoloration plays an important role in self-perception. Discoloration, dark spots, and uneven skin tone are among the most prevalent skin conditions for which consumers seek treatment. While certain pigmentary disorders may arise from genetic origins, many forms of discoloration are exacerbated by endogenous or exogenous stimuli, such as UV radiation, inflammation, hormonal fluctuations, or the natural aging process. Despite a great consumer demand, topical formulations proven effective in the treatment of discoloration are lacking.

In order for a topical treatment to successfully address a wide range of stubborn brown patches, it is crucial that the formulation contain ingredients that target multiple biological pathways associated with the development of unwanted discoloration. Inhibition of melanin synthesis, inhibition of melanosome transfer to keratinocytes, or enhancement of cellular turnover and exfoliation are all known strategies for reducing cutaneous discoloration. Recently the prevalent role of inflammatory mediators in the melanogenesis process has been more clearly elucidated.  Inflammatory mediators act upstream, increasing melanocyte activity and the appearance of discoloration.

The most widely used discoloration treatments target melanocyte activity, tyrosinase activation, or melanocyte transfer, ignoring the critical stage of early inflammation. Moreover, new studies show that deactivating upstream inflammatory mediators can prevent and correct discoloration, including difficult-to-treat forms, such as melasma. Incorporation of ingredients targeting certain inflammatory pathways appears to be a promising approach for reducing the appearance of discoloration.

SkinCeuticals Discoloration Defense is formulated with the latest generation of discoloration-fighting ingredients, targeting diverse pathways implicated in the appearance of pigmentation. Tranexamic acid (TXA) inhibits the release of inflammatory mediators, kojic acid suppresses melanin synthesis, niacinamide reduces melanosome transfer, and HEPES offers exfoliating and hydrating benefits. Formulated in a pleasant multi-phase serum texture, this combination helps reduce the appearance of discoloration, including stubborn cases, such as melasma and post-inflammatory hyperpigmentation.

What are the typical causes of skin discoloration that bring patients to the office?

Sarah Sawyer, MD: I classify discoloration into categories of “red” and “brown” pigmentation. Ninety percent of the time, patients present to me with unwanted brown patches on the face. Skin discoloration can be genetic and exaggerated by exposure to atmospheric insults, including ozone, ultraviolet, and infrared irradiation. More severe discoloration, including post-inflammatory hyperpigmentation (PIH) or melasma, also represent aesthetic concerns for many patients. Melasma can be exacerbated by additional factors, such as intrinsic hormones—which may be secondary to pregnancy, birth control, or thyroid disease. Postinflammatory hyperpigmentation is associated with several skin conditions and may occur following insult to the skin, including non-ablative or ablative laser procedures performed at home or in the office.

We continue to gain increasing clinical evidence to support that even limited exposure to UV or hormone fluctuation may cause the patient to experience inflammation resulting in worsening of skin discoloration.

What are the conventional topical approaches to management? Why may they be insufficient to manage skin discoloration?

Dr. Sawyer: If you are a physician who does not typically implement laser procedures, your first move may be to target pigmentation by treating patients with a high dose of hydroquinone and retinol or tretinoin. We now realize there are limitations to this approach. Discoloration often flares when coming off hydroquinone; in some cases this worsens skin tone unevenness.

There is also evidence supporting a role for hydroquinone in the activation of inflammatory mediators in the skin, especially at high doses. Similarly, topical retinoids used long-term may induce localized inflammation.

What is the role for procedural treatments?

Dr. Sawyer: Energy-based laser procedures have emerged as an opportunity to treat unwanted discoloration. Skin ablation works to create a targeted, controlled wound, characterized by secondary inflammation that reduces the appearance of pigmentation.

However, inflammation can be exacerbated by exposure to UV radiation, particularly during the summer months or in warmer climates with higher daily solar exposure. In addition, procedures may also be relatively expensive for patients purchasing a treatment series.

What are key ingredients in Discoloration Defense?

Dr. Sawyer: This formulation contains 3% tranexamic acid (TXA). TXA is a synthetic analog of the amino acid lysine that competitively inhibits the transformation of plasminogen to plasmin, a molecule that degrades fibrin.^1-3 TXA has historically been used as an anti-fibrinolytic agent for patients with menorrhagia and in open-heart surgery. Its use in treating melasma was first reported in 1979 when it was observed that patients treated with oral TXA for chronic urticaria demonstrated improvement of their discoloration.

More recently, there have been numerous studies proving TXA's efficacy when administered orally or applied topically in treating hyperpigmentation in the skin.

Tranexamic acid can also be used in conjunction with other topical ingredients including niacinamide as an alternative to hydroquinone. The dermatological benefits of topical niacinamide (formulated at 5% in Discoloration Defense) have been well studied and documented. Given appropriate concentration and sufficient cutaneous exposure, niacinamide is known to have antipruritic, anti-inflammatory, antimicrobial, and sebostatic properties. Niacinamide has been commonly associated with skin lightening benefits.^4,5

Kojic acid (1%) is a naturally occurring fungal metabolite and has become a well-known inhibitor of tyrosinase, a key enzyme in the melanin production pathway. Kojic acid has been evaluated for the treatment of melasma and proven effective in reduction of pigmentation.^6,7

The formulation also contains 5% HEPES, an enzymatic exfoliator that enhances the natural desquamation process and promotes cellular turnover.

How do you recommend patients use Discoloration Defense?

Dr. Sawyer: This formulation offers a multi-modal approach to treating unwanted discoloration. Patients prefer a product to multi-task, because both financially and practically, we aim to limit the number of products applied in the morning and at night.

Discoloration Defense can be used as a standalone or introduced as a 1.) priming product before treatments, as a 2.) maintenance solution between treatments, or 3.) long-term solution post-treatment to help preserve results. Discoloration Defense is proven safe and well tolerated. In addition, Discoloration Defense is a serum that dries quickly with a clean finish, upon which one may apply makeup. In my experience, it is effective for patients with sensitive skin.

For the management of discoloration flare-up, Discoloration Defense can be applied twice daily and is best paired with SkinCeuticals antioxidants (C E Ferulic or Phloretin C F), and sunscreens (Light Moisture UV Defense SPF 50).

I believe Discoloration Defense is safe and effective for the treatment of unwanted discoloration in patients wanting brighter-looking skin with improvements of overall skin texture and tone. It is great as a starter multi-phase serum or as a product to add to an existing discoloration regimen.

1. Tse, T. W.; Hui, E. Tranexamic acid: an important adjuvant in the treatment of melasma. J. Cosmet. Dermatol. 2013, 12, 57-66.

2. Kim, H. J.; Moon, S. H.; Cho, S. H.; Lee, J. D.; Kim, H. S. Efficacy and safety of tranexamic acid in melasma: A meta-analysis and systematic review. Acta Derm. Venereol. 2017, 97, 776-781.

3. Taraz, M.; Niknam, S.; Ehsani, A. H. Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies. Dermatol. Ther. 2017, e12465.

4. Hakozaki, T.; Minwalla, L.; Zhuang, J.; Chhoa, M.; Matsubara, A.; Miyamoto, K.; Greatens, A.; Hillebrand, G. G.; Bissett, D. L.; Boissy, R. E. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br. J. Dermatol. 2002, 147, 20-31.

5. Wohlrab, J.; Kreft, D. Niacinamide – mechanism of action and its topical use in dermatology. Skin Pharmacol. Physiol. 2014, 27, 311-315.

6. Lim, J. T. Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. Dermatol. Surg. 1999, 25, 282-284.

7. Garcia, A.; Fulton, J. E. The combination of glycolic acid and hydroquinone or kojic acid for the treatment of melasma and related conditions. Dermatol. Surg. 1996, 22, 443-447.

PRODUCT SPOTLIGHT

Discoloration Defense

• Layerable, daily-use dark spot corrector
• 3% tranexamic acid
• 1% kojic acid
• 5% niacinamide
• 5% HEPES
• Paraben-, fragrance-, silicone-, gluten-, and hydroquinone-free

In a 12-week clinical study, subjects had a 60% average improvement in the appearance of stubborn brown patches and a 59% average improvement in the appearance of skin discoloration.