Melasma is a skin pigmentary disorder affecting millions of patients worldwide. Melasma is characterized by patterns of patchy hyperpigmentation, usually on the cheeks, under the eye, upper lip, and forehead. Skin discoloration associated with melasma is due to an over accumulation of skin pigment melanin, is produced by pigment cells called melanocytes. Although etiology of melasma is largely unknown, it is understood that genetics plays the largest role. Melasma can be further exacerbated by UV exposure, heat and visible light.  Occurrence of melasma is often linked to hormonal triggers like oral contraceptive pills, IUDs, hormone therapy and pregnancy.

Melasma can be categorized as “epidermal” or “dermal”, or mixed.

In epidermal melasma melanin is present in the more superficial epidermal layers

In dermal melasma melanin is in the deeper layers of the skin and is typically visualized best under Wood’s lamp examination. This distinction is crucial because epidermal melasma responds more quickly to treatment.  Dermal melasma is much more difficult to treat.

Mixed melasma is a combination of epidermal and dermal melasma.  Melasma is often associated with increased vascularization ie. increased number of blood vessels, vessel size, and vessel density.

When treating pigmentary disorders it is important to be evaluated by a board-certified dermatologist to first accurately diagnose melasma as an underlying cause of hyperpigmentation and second to determine melasma subtype prior to pursuing any treatments or products as some treatments might significantly worsen melasma.

Treatment for Melasma

The management of melasma is often challenging, with partial responses and frequent relapses. A combination of therapies targeting multiple pathogenic elements, such as photodamage, inflammation, aberrant vascularity, and abnormal pigmentation, generally provides the best clinical outcomes. The best therapeutic armamentarium includes a variety of agents that

• inhibit the biosynthesis of melanin
• increase skin epidermal turnover and therefore removal of excess of melasma pigmentation
• chemical peels and lasers that directly remove of excess melanin

Sun Protection

Sunscreens are essential to prevent progression of melasma due to UV exposure, visible light, and blue light from electronic devices. The best sunscreen for melasma is physical sunblock with SPF 30 or higher that contains zinc oxide or titanium dioxide as the active ingredient.

Lasers

NeoClear by Aerolase

The NeoClear by Aerolase® has proven to be effective against both dermal and epidermal melasma. This laser targets pigment/melanin itself, without causing any additional tissue damage and without any risk of post-inflammatory hyperpigmentation or pigmentation worsening. This makes 1064 lasers an ideal choice in melasma treatment, as many other treatments (including both topicals and other lasers) result in tissue inflammation. Also unlike other lasers, due to its 650 – microsecond technology the laser can effectively penetrate to the deeper layers of the skin ie. dermal layers treating dermal melasma and melasma associated increased vascularity  without risk of tissue damage.

Clear + Brilliant, Permea

Clear + Brilliant is a non-invasive laser that creates thousands of “micro injuries” to the epidermis. These micro-injuries trigger the body’s healing process, replacing damaged cells with new, healthy tissue.  Clear and Brilliant resurfacing also allows for optimal penetration of products that help to reduce pigmentary change.  Clear + Brilliant is the most gentle fractional resurfacing laser (treating up to 20% of the skin), which is optimal for those who are looking to minimize downtime or those who have milder cases of melasma. Multiple sessions are required to achieve clinical reduction of melasma.

Fraxel DUAL 1550/1927 Fractional Resurfacing

Fraxel is a non-ablative fractional resurfacing laser that creates microthermal injury zones in the skin to stimulate the body’s own healing and rejuvenating process.  The procedure targets a portion of tissue at a time, leaving the surrounding tissue enact. As this laser does not cause complete tissue damage, the laser itself can remove tissue containing melanin pigment. Fraxel is from the same family as Clear + Brilliant, however Fraxel targets a larger percentage of skin tissue (treating up to 40% of the skin). This is an optimal treatment option for patients who are comfortable with having more downtime as well as patients with a most severe melasma.

Coolpeel CO2 Resurfacing, Lumenis UltraPulse CO2 Ablative Resurfacing

Considered one of the most intensive resurfacing lasers, the CO2 laser is an ablative fractional laser. By comparison to the other lasers in this category, the CO2 laser removes via vaporization the outermost (epidermal) layers of skin cells, relying on the dermal tissue beneath to initiate a healing response. This again creates new, healthier tissue that is free of pigmentary changes or evidence of UV damage. These lasers not only target the melanin pigment in the epidermal skin layers, but can also target the pigment producing melanocytes. This laser is extremely efficacious, but requires the most significant amount of downtime. This laser is ideal for patients who are comfortable with extended periods of downtime as well as patients with stubborn, resistant melasma that has not responded with more conventional laser therapies.

Oral medications

Tranexamic acid- which has been shown to be effective in the treatment of melasma. The largest study on the use of oral tranexamic acid for treatment of melasma was a retrospective review of 561 melasma patients treated with tranexamic acid.  More than 90% of patients received prior treatment for their melasma, including bleaching creams and laser treatments. Among patients who received oral tranexamic acid over a 4-month period, 90% of patients demonstrated improvement in their melasma severity. Tranexamic acid has been shown to be safe but is not recommended for a long term use. It is also contraindicated in patients with personal or family history of clotting disorders, personal history of deep vein thrombosis (DVT), or patients who are currently pregnant or are preparing to conceive.

CHEMICAL PEELS

Chemical peeling involves the topical application of a chemical agent, wherein the desired outcome is a controlled regeneration of the skin and removal of excess pigmentation.

Cosmelan depigmenting solution by mesoestetic offers a professional depigmenting protocol designed to eliminate or reduce dark spots while unifying the skin tone and enhancing overall skin luminosity.

Topical skin care

There are many active ingredients used to improve existing hyperpigmentation of melasma. The most common and effective ones are hydroquinone (HQ), kojic acid, azelaic acid, ascorbic acid/Vitamin C, glycolic acid (AHA or alpha hydroxy acids), tranexamic acid, licorice root extract, and Vitamin A derivatives (ie retinol, all-trans retinoic acid). Most of these ingredients work mostly by either inhibiting melanin synthesis or exfoliating excess of superficial pigmentation.

• HQ- Of the components mentioned above HQ has shown to be one of the most effective topical treatments and is widely considered the gold standard in clinically reducing the appearance of melasma. However, due to its strong effects on skin cells, HQ should not be used for long periods of time, and the recommended duration should not exceed more than 3-6 months of continuous use.
• Vitamin A (Retinoids, Retinols) – Acts by tyrosinase inhibition, preventing melanosome transfer, and increases epidermal turnover, by essentially “ungluing” the bonds that hold damaged, melanin-containing skin cells and effectively exfoliate these dead skin cells. Cellular turnover by using vitamin A is typically seen over a period of 28 days, however increased use of vitamin A has shown to increase the rate of cell turnover to 21 days or even 18 days. Vitamin A on its own and the combination of vitamin A + HQ can be very irritating and drying on the skin, so these medications are often compounded further with a corticosteroid (commonly called triple combination or TC therapy) to help reduce inflammation resulting from these active ingredients. They also make your skin increasingly photosensitive, which further stresses the importance of daily sunscreen with SPF of 30 or higher.
• Vitamin B3 (Niacinamide) – Studies have shown that Vitamin B3 may decrease skin pigmentation by preventing melanosome transfer within skin cells. It also plays a role as both an antioxidant and an anti-inflammatory. Similarly to Vitamin C, Vitamin B3 neutralizes reactive oxygen species (ROS). As an anti-inflammatory, Vitamin B3 can effectively reduce the inflammatory response from intensive active ingredients such as HQ and Vitamin A.
• Vitamin C (Ascorbic Acid) – Another tyrosinase inhibitor, widely used in skincare as a potent antioxidant and for its skin “brightening” abilities. Vitamin C also donates electrons to neutralize reactive oxygen species (ROS) that are generated due to UV exposure. Harmful ROS occur when there are alterations of cellular DNA, the cell membrane, and cellular proteins (including collagen).
• Alpha Hydroxy Acids (Lactic Acid, Glycolic Acid, Mandelic Acid) – Water loving acids derived from a natural substance (sugar cane, milk, almonds, grapes), most effective for surface level pigmentary changes. The large molecular size allows penetration to be limited to the epidermis. AHA’s assist in superficial skin turnover and allow the skin to shed spent cells to reduce the appearance of pigmentation.
• Beta Hydroxy Acid (Salicylic Acid) – Oil loving acids that penetrate deeper into the skin through bypassing the oil that clogs pores and dissolve the mix of sebum and dead skin as well as stabilizing the lining of the pore. Unglue the bonds holding dead skin to the surface and allow the skin to shed spent cells to reduce the appearance of pigmentation.
• Azelaic Acid – Recent studies have shown that Azelaic Acid is an effective tyrosinase inhibitor and continuous use has been shown to reduce clinical appearance of melasma and pigmentary changes. Azelaic acid, however, must be used in a high enough concentration for maximal effectiveness (between 5-20%).
• Ferulic Acid – Ferulic acid may work minutely to prevent melanin formation, but where it really stands out as an active ingredient is it’s effects on other skin ingredients. When combined with other actives (such as Vitamins A, C, and E), it enhances the effectiveness of these ingredients. Especially in the case of Vitamin C (which is an excellent skin ingredient, however it’s effectiveness is often deterred by it’s instability) where ferulic acid helps to stabilize the molecule from degrading and also increase its photoreceptiveness (i.e. the ability to minimize sun damage).
• Kojic Acid – A tyrosinase inhibitor produced by several fungi species.
• Cysteamine – At high concentrations, cysteamine has been shown to inhibit melanogenesis. Cysteamine may also have anti[cancer and anti-melanoma effects for added benefit by comparison to some other active ingredients. Cysteamine by comparison has similar side effects to HQ (including skin irritation, dryness, etc.) but otherwise proves to be safe for use.
• Epidermal Growth Factor (EGF) – A tyrosinase inhibitor which has been shown to gently and safely improve pigmentary changes.
• Tranexamic Acid – Tranexamic acid (TXA) is a fibrinolytic agent that blocks the plasmin pathway and can be delivered in various forms (oral, topical, intradermal). Knowing that an increased vascular component is observed histologically in those with melasma, TXA has shown to significantly reduce the appearance of melasma. TXA modulates the blood vessels and vascularization to the melanocyte itself, which can thereby reduce melanin output. All three have been studied in relation to their effects on melasma,, with oral formulations demonstrating the greatest improvement in patients. All three forms have shown in recent studies to improve melasma and quiet possibly have equal effects to HQ. Side effects of TXA are often related to large doses (to treat blood disorders such as hemophilia), which are vastly larger than the doses given to treat melasma. Dosing of TXA should always be consulted with a physician prior to use.
• 4-n-butylresorcinol – A tyrosinase inhibitor that has been shown to reduce hyperpigmentation and melasma related skin changes when applied at low concentrations with minimal to no skin irritation in recent studies.

Microneedling

Microneedling has been proven to have many anti-aging and skin rejuvenating benefits. Microneedling helps to create micro injuries within the skin to stimulate the healing response, promoting new, healthier tissue with more uniform pigmentation. The creation of these microscopic “tunnels” from the microneedling act as effective passageways to maximize the penetration of topical ingredients beneficial in management of melasma

As melasma is a chronic condition, it is widely accepted that a combination of all the aforementioned treatments (sun protections, topical remedies, laser treatments) offers most benefits. Melasma is often a lifelong condition, but it can be effectively controlled with continuous use of topical treatments ad regular maintenance with laser therapy.