Pearl E. Grimes, M.D., discusses the complexities of melasma and the need for a multimodal treatment approach.
Melasma: It’s complicated. It’s a unique form of photodamage that can have a vascular component, and new non-hydroquinone options are helping to address treatment gaps. But we do not yet have an optimal, effective and long-term treatment, according to dermatologist Pearl E. Grimes, M.D.
“Melasma is far more complex than we ever realized. As we get more data and look at pathogenesis pathways, we realize the true complexity of the condition. We know there’s a complex interplay of genetics, sun exposure, hormonal influences - even medications can trigger melasma,” says Dr. Grimes, who directs the Vitiligo and Pigmentation Institute of Southern California and is a clinical professor of Dermatology at UCLA. She presented on melasma at the 2019 American Academy of Dermatology annual meeting.
Melasma’s Link to Photodamage
Studies in recent years have revealed that melasma represents a unique phenotype of photodamage, which could signal a big shift in how dermatologists treat melasma, according to Dr. Grimes.
Melasma studies show, for example, that biopsies of the involved skin show an increase in solar elastosis, compared to uninvolved skin. Researchers have found that melasma biopsies exhibit damage to the basement membrane, which affects collagen. Biopsies of involved skin also show an increase in mast cells compared to those of normal skin. And there is a cohort of patients who have vascular melasma, where dermatologists see an increase in blood vessels and increased vascular endothelial growth factor (VEGF) in the affected versus nonaffected skin.
“All of this suggests it’s a form of photodamage,” Dr. Grimes says.
Moreover, involved skin areas show senescent fibroblasts.
“We also know that if you look at the pathways of what is upregulated in melasma lesions, there’s crosstalk between what is occurring in the epidermis and what’s happening in the dermis, as well,” she says. “The dermis and the epidermis are both impacting melanocytes and melanogenesis. Sunlight stimulates keratinocytes in the epidermis to release growth factors, such as stem cell factor, endothelin 1, alpha-melanocyte stimulating hormone (MSH), nerve growth factor - all are upregulated in melasma-affected areas. From the dermis, fibroblast growth factor and stem cell factor are upregulated. All of these cytokines are speaking to each other, and they’re upregulating pigment production in melanocytes.”
A Multimodal Treatment Approach
As a result, dermatologists should look at treating melasma through a multimodality lens, according to Dr. Grimes.
“We can’t be myopic and look at it from the perspective of just using a lightener. I think we have to approach it from the perspective of treating photodamaged skin, as well as reducing pigmentation,” she says.
That’s not to say that hydroquinone doesn’t have a role in melasma treatment.
“If you look at where we are today with non-hydroquinone products, versus where we were five years ago, there’s a trend to move beyond hydroquinone if we can. Now we have non-hydroquinone products that really do have the ability to significantly reduce melanin,” Dr. Grimes says. “But I think that if you have a really stubborn case, we still need hydroquinone.”
Dr. Grimes says there is a great need for sunscreens that block not only ultraviolet but also visible light.
“We know about UV exposure, but we’ve missed the role of visible light in melasma. There have been some interesting studies showing that visible light can trigger pigmentation particularly in darker skin. And there are several studies now that show that when you use an iron oxide sunscreen that blocks visible light, melasma patients get much better,” Dr. Grimes says.
Part of the dermatologist’s multimodality approach to melasma treatment might also include oral agents, according to Dr. Grimes.
“Heliocare (polypodium leucotomos) has taught us the importance of oral antioxidants as stabilizers and adjunctive antioxidants in the treatment of melasma. We may well see more oral agents,” she says.
Dr. Grimes says there are many options for addressing melasma’s vascular component but none are ideal. She says she’ll use some topicals to shrink the blood vessels, such as topical tranexamic acid or brimonidine, commonly used to treat rosacea.
Tranexamic acid, which is gaining popularity as a melasma treatment, lacks long-term data in melasma, according to Dr. Grimes. She says she’s also concerned about using oral tranexamic acid in patients who might have an underlying predisposition for thromboembolic phenomena.
“I have a few patients on oral tranexamic acid, but I use much more topical tranexamic acid than oral. I mix and match the tranexamic with other topicals. I even use it in combination with hydroquinone for patients with stubborn cases of melasma,” Dr. Grimes says.
The pulse dye laser works well to treat the vascular component, but dermatologists can’t use the pulse dye laser on darker skin tones. And intense pulsed light (IPL) might help some patients, says Dr. Grimes, but dermatologists have to beware that in dark skin types, IPL can worsen melasma.
Today’s better understanding of melasma’s pathophysiology will create a foundation for more targeted treatments, Dr. Grimes asserts.
“We still need treatments that are safe and effective that offer long-term remission control. That’s what we continue to struggle with. You can have a patient who looks great on Friday, and if they get sun exposure, they’re back to square one on Monday,” she says. “I think that’s a major area where these new generation photoprotection agents will help us out. I want to have something that puts the patient in remission for a year.”
Dr. Grimes receives grant/research/clinical trial support from: Galderma, Allergan/SkinMedica, Procter & Gamble, Clinuvel, Merz, Valeant, L’Oreal, Johnson & Johnson, Suneva, LaserOptek, VT Technologies, Incyte, Aclaris, Pfizer, Thync, and Dermaforce. She is a consultant/advisory board member for VT Technologies and Dermaforce.