Melasma

Melasma

Melasma is a dysregulation of the homeostatic mechanisms that control skin pigmentation and excess pigment is produced. Traditional treatment approaches with topical medications and chemical peels are commonly used but due to the refractory and recurrent nature of melasma, patients often seek alternative treatment strategies such as laser and light therapy. Several types of laser and light therapy have been studied in the treatment of melasma. Intense pulsed light, low fluence Q-switched lasers, and non-ablative fractionated lasers are the most common lasers and light treatments that are currently performed. They all appear effective but there is a high level of recurrence with time and some techniques are associated with an increased risk for postinflammatory hyper- or hypopigmentation. The number and frequency of treatments varies by device type but overall, Q-switched lasers require the greatest number of treatment applications to see a benefit.
Melasma is a common and well-described dermatological condition that primarily affects female patients. It involves hyperpigmentation that is chronic, relapsing, and characterized by symmetric, brownish-grey macules and patches on the face and sometimes the neck, chest, and forearm. Melasma has also been referred to as chloasma or “the mask of pregnancy” because the condition is often associated with women who are pregnancy. The condition is otherwise asymptomatic and there is no clear association with a systemic illness but melasma can be psychosocially detrimental to many patients.

There is currently no definite etiology but multiple factors including ultraviolet radiation, hormonal alterations within the estrogen or progesterone pathways, genetic predisposition, and/or inflammation have all been implicated and recently reviewed.

The common outcome from these diverse triggers is an increased synthesis of melanosomes in melanocytes and an increased transfer of melanosomes to keratinocytes. Women with darker skin types (i.e., Fitzpatrick skin type IV-VI) are most commonly affected.

Treatment strategy

The treatment regimen of patients with melasma typically starts with the management or elimination of risk factors, strict ultraviolet sun protection, and topical lightening formulations. Topical treatments may temporarily improve the skin but the condition often returns. The principles of therapy include the inhibition of pathways that synthesize melanin, decrease of melanosome transfer from melanocytes to keratinocytes, and acceleration of pathways to remove melanin.
The current first-line treatment for melasma is topical agents. The major group of topical agents to be considered are those that disrupt the enzymatic processes of pigment production within melanocytes. These types of treatments include hydroquinone.

Other targets for intervention in the melanin synthetic pathway include the interaction between keratinocytes and melanocyte. There are several botanical agents such niacinamide and soy that act through protease-activated receptor-2 and inhibit the transfer of melanosomes to the surrounding keratinocytes. Serine protease inhibitors, lecthins, and neoglycoproteins also affect this pathway.

Improving skin turnover is another therapeutic route for the treatment of melasma. Agents that accelerate skin turnover include glycolic acid, linoleic acid, lactic acid, liquiritin, retinoic acid, and Helix aspersa müller. Certain fatty acids such as linoleic or α-linoleic acid may induce the degradation of tyrosinase.

Topical treatments may be unsatisfactory due to a lack of response, slow rates of improvement, or adverse events such as pseudo-ochronosis with hydroquinone or skin irritation, erythema, and postinflammatory hyperpigmentation.

Chemical peels

The addition of chemical peels to a topical treatment regimen is second-line treatment as peels help accelerate the elimination of pathways for melanin. Superficial peels such as glycolic acid, Jessner, and retinoic acid are typically selected because they tend to have the least risk of complications and exacerbation of pigmentation if there is too much inflammation or irritation. Peels have been shown to be effective, especially when used in a series of treatments. Chemical peels may cause melasma rebound or PIH due to irritation or inflammation.

Laser- and light-based treatments

Laser and light therapy represent an alternative third-line approach to treat melasma and may be particularly beneficial for patients with melasma that is refractory to topical therapy or chemical peel regimens, or when a patient wishes for an accelerated pace of improvement. Analogous to chemical peels, these modalities accelerate the removal of pathways for melanin but do not target the melanin production itself. One key point of patient counseling prior to laser- and light-based treatment is that these therapies have the potential to speed up the removal of melasma-related hyperpigmentation but they are not cures for melasma. Furthermore, they present a risk for PIH or a rebound melasma flare.

Optimal treatment management of difficult cases should include a combination therapy whereby a topical regimen inhibits melanin production and/or melanosome transfer and a procedure accelerates melanin removal.

Table 1. Proposed therapeutic ladder for melasma

First-line Therapy	Control of risk factors (sun protection, discontinue hormone treatments or photosensitizing medications) -Topical anti-Tyrosinase therapy -Other inhibitors of the melanin synthetic pathway(e.g., protease-activated receptor-2 inhibitor) -Topical exfoliant -Triple combination topical cream, if tolerated
Second-line Therapy	Combination of first-line treatments + series chemical peels
Third-line Therapy	Combination of first-line treatments with: -NAFL (1927 nm) -NAFL (1550 nm, 1540 nm, or 1440 nm) -Fractional radiofrequency devices
Fourth-line Therapy	Combination of first line treatments with: -Intense pulsed light (test spots) -Q-switch laser

Table 2. Proposed pretreatment regimen

Two to Six Weeks Pretreatment

Control of risk factors (sunprotection, discontinue hormone treatments) with: -Topical anti-Tyrosinase therapy daily -Other inhibitors of the melanin synthetic pathway (e.g., protease-activated receptor-2 inhibitor)

Table 3. Proposed post-treatment regimen

Immediate Posttreatment	Topical Tyrosinase inhibitor immediately posttherapy High potency topical corticosteroid two times daily for 3 days postprocedure
Two Weeks Posttreatment	Control of risk factors (sun protection, discontinue hormone treatments) with: -Topical anti-Tyrosinase therapy daily -Other inhibitors of the melanin synthetic pathway (e.g., PAR-2 inhibitor)
Long-term Posttreatment	Control of risk factors (sun protection, discontinue hormone treatments) with: -Topical anti-Tyrosinase therapy daily -Other inhibitors of the melanin synthetic pathway (e.g., PAR-2 inhibitor) -Resume topical exfoliant daily, if tolerated -Resume triple combination topical cream, if tolerated

Light and laser therapy is an alternative approach to treat patients with recalcitrant melasma. The current methods are limited by recurrence, postinflammatory dyspigmentation, and the need for multiple treatments. However, as the treatments transitioned from Q-switched lasers and IPL to NAFL, the recurrence rate and number of treatments necessary to see benefits have decreased. The treatment will continue to evolve as advances in laser or device technologies emerge. Imaging and drug delivery methods can enhance these technologies, and it will be interesting to see how the picosecond lasers and fractional radiofrequency devices will impact melasma treatments.

Each case should be evaluated individually and a selected treatment should be planned for each case.

Every patient should consider all options and be aknowledged thet it requires time, structural steps and procedures to reach optimal results along the way.