Feedback AAD 2017

Where Do We Stand? The Pathogenesis and Treatment of Melasma

Melasma and vitiligo are psychologically devastating diseases that can greatly impact the personal well-being and quality-of-life of those patients suffering from the disease. As major research on melasma has shown, its pathological basis can be quite complex and may possibly be one of the most difficult pigment related disorders treated by dermatologists, as stated by Pearl Grimes, founder and director of the Vitiligo and Pigmentation Institute of Southern California and clinical professor, Division of Dermatology at the David Geffen School of Medicine in UCLA, Los Angeles, California, USA.

Patients with melasma (Figure) have demonstrated a number of abnormal findings, including the presence of solar elastosis, increase in dermal blood vessels, increased expression of vascular endothelial growth factor, altered barrier function of the skin, and abnormal basement membrane. In addition to hormonal dysfunction, in most patients there is an increase in melanogenesis without an increase in the number of melanocytes, and accumulation of epidermal and dermal melanin. These findings suggest that patients may have both epidermal and dermal melasma. The role of sunscreens in the treatment of melasma is undisputable.

New changes in sunscreen components have provided an addition to the arsenal for the treatment of melasma. As photoprotection and the avoidance of sun exposure are the first line of defense, Ivonne Arellano-Mendoza, from the Hospital General de Mexico, Mexico City, Mexico described some of the sunscreen key players in regards to organic and inorganic topicals. Most notably, some inorganic sunscreen products now contain micronized titanium oxide or zinc oxide which are able to scatter and reflect light as well as absorb ultraviolet light. As organic filters do not protect from visible light, this is an important finding to help minimize exposure to light and ultraviolet radiation.

It is important to note the immunological and other biological responses that were present with exposure to infrared radiation and the visible light spectrum. For example, there was an increase in matrix metalloproteinase (MMP)-1 and MMP-9 expression, a collagenase and gelatinase respectively. In addition, exposure to infrared radiation and the visible light spectrum induced macrophage infiltration as well as encouraged the production of reactive oxygen species (ROS), proinflammatory cytokines, and the MMP-1. However, pretreatment with a photostable sunscreen containing antioxidants reduced ROS and MMP-1 production by 78% and 87% respectively in in vitro studies.

Topical therapies continue to be the baseline treatment options for melasma says Seemal Desai, a clinical assistant professor in the Department of Dermatology at the University of Texas Southwestern Medical Center in Dallas, Texas, USA.

Desai also discussed the need to be more vigilant in terms of accurately diagnosing melasma as not all cases of facial hyperpigmentation or facial hypermelanosis are melasma. Hypermelanosis can encompass a variety of conditions aside from melasma. In terms of workups, it is important to remember that melasma has some correlation to metabolic conditions such as thyroid dysfunction and hypercortisolemia. In patients where a complete history is not known, ie such as with possible hormonal fluctuations or drug-induced metabolic dysfunctions, work ups using laboratory testing is an option for a more definitive diagnosis.

Desai stressed the importance of speaking with patients in terms of the sequence of events in melasma, knowing that it is a chronic and resistant skin condition. In addition, it is important to explain to patients with melasma, that there is a high rate of recurrence and a complete cure is unlikely. While this approach may seem somewhat brash and abrasive, it is important to set realistic expectations and provide honest counsel to patients. In terms of the standard of care, triple combination therapy remains the most frequently used topical therapy in the treatment of melasma. It has proved successful as a first line therapy in a study of approximately 600 patients with skin type 4, 5, 6 where patients were randomized to either the triple therapy arm or to hydroquinone alone. Assessment via melasma GSS (Global Severity Score), MASI (Melasma Area and Severity Index), and patient satisfaction were all statistically greater than that of the hydroquinone group alone. The results of this study suggest that monotherapy of hydroquinone is not the best option for the treatment of patients with melasma.

Azelaic acid is a treatment option that can be used during the hydroquinone holiday period. It is capable of lightening pigment, although it will not be as strong in reducing the melasma index scores compared to hydroquinone. Azelaic acid is a tyrosinase and mitochondrial respiratory enzyme inhibitor that has minimal side effects of erythema, pruritus, and burning. It has a pregnancy category B warning which allows dermatologists to use this in patients who are pregnant or trying to conceive. Kojic acid is another option that may be used in combination with hydroquinone, but not as monotherapy.

Topical zinc formulations are another option. However, they are not used in a lightening capacity, but instead, as an epidermal exfoliator which can reduce melanin. Arbutin is a botanical option that may be suitable for patients unwilling to use prescription medications. It is a derivative from the cranberry and blueberry shrub and functions as a tyrosinase inhibitor. Vitamin C deserves to be mentioned as an antioxidant, however, it is not stable when placed on the skin in its pure form. Nevertheless, when used in tandem with hydroquinone or with sunscreen products, an improvement can be seen. Soy has also been shown to have beneficial lightening properties. It has multiple properties, such as the inhibition of PAR-2 and melanosome transfer, the inhibition of trypsin which would activate PAR-2, and the inhibition of DOPA oxidase activity.