Melasma may require aggressive combination therapy

Denver - Successfully treating melasma requires a correct diagnosis and, increasingly, combination therapy, an expert says.

To prevent misdiagnosing melasma, dermatologists must remember that melasma does not usually affect the eyelid area, says Amit Pandya, M.D., professor of dermatology, University of Texas Southwestern, Dallas.

“It does not go above the inferior orbital rim, or below the superior orbital rim. It stays outside the lateral canthus,” he says.

Melasma usually gravitates toward the central forehead, he notes. “It also emanates above the eyebrows and stops somewhere on the forehead instead of continuing from the eyebrows all the way to the hairline,” Dr. Pandya says. Lesions on the lateral forehead are more likely to be lichen planus pigmentosus, he says.

Eyelid lesions, however, usually represent periorbital hyperpigmentation.

“Additionally, melasma tends to spare the nasolabial folds. But it has a predilection for the upper lip,” he says. For hyperpigmentation of the nasal tip, consider an adverse drug reaction, such as minocycline-induced pigmentation, rather than melasma.

Additionally, “We know that dermal pigmentation is found in all patients with melasma (Grimes PE, Yamada N, Bhawan J. Am J Dermatopathol. 2005;27(2):96-101). So when you use a Woods lamp and conclude that a patient has superficial epidermal melasma, you may be fooling yourself. There are actually dermal melanophages there - we just can’t see them very well with the Woods lamp,” Dr. Pandya says.

Dermatologists who treat Asian patients must rule out acquired bilateral nevus of Ota-like macules (Hori’s nevus), Dr. Pandya says. This entity afflicts 4.2 percent of Chinese women and is characterized by melanocytes in the dermis that can be treated with laser, he adds. Dot-like macules on the cheek, often grayish, also can help identify Hori’s nevus, Dr. Pandya says.

“Melasma usually cannot be treated with laser because it involves melanophages in the dermis, which do not respond well to laser, whereas melanocytes will respond,” he says.

Blocking visible light

Although UV light plays a major role in the etiology of melasma, he notes, one study also implicates visible light (Mahmoud BH, Ruvolo E, Hexsel CL, et al. J Invest Dermatol. 2010. 130;2092-2097). This study showed that visible light can induce pigmentation in patients with skin type V, but not type II. For darker skinned patients, “This is bad news. We have sunscreens that cover UVA, UVB and UVA1, but none that cover above 400 nm,” Dr. Pandya says. Accordingly, if a patient works at a computer screen or simply steps outside, “Visible light is streaming down. And this may be one of the reasons why melasma is so difficult to treat.”

In a 20-patient study, researchers attempted to block visible light with sunscreens containing varying amounts of iron oxide.

“They gave subjects aminolevulinic acid, applied sunscreen and saw the patients 18 hours later and calculated minimum phototoxic doses (MPD) using visible blue light. They found the MPD was two for patients who had received iron oxide 0.2 percent and 21 for those receiving iron oxide 3.2 percent (Bissonnette R, Nigen S, Bolduc C, et al. Dermatol Surg. 2008;34(11):1469-1476). This means we now have something that will block visible light - iron oxide accounts for the brownish color we see in tinted sunscreens and mineral makeup,” Dr. Pandya says.

“Patients with melasma tend to have the disease for a long time. We’ve always been told to treat it for six months, and it’s gone,” he says.

Next: Care over the long term

Focus on the long term

Studies and his clinical experience indicate, however, that patients can have melasma for 10 to 12 years, Dr Pandya says. “It will go away after pregnancy, but sometimes it will recur when a woman is in her 30s and won’t resolve until menopause.”

Accordingly, he says that he treats difficult cases of melasma as though it were a chronic condition such as diabetes (Sheth VM, Pandya AG. J Am Acad Dermatol. 2011;65(4):689-697). When lesions resolve after three to six months of treatment, for example, “I drop patients down to formulas containing kojic acid, arbutin, azelaic acid or 2 percent hydroquinone. When melasma returns in the summer, I go back up to stronger agents,” he says.

Hydroquinone alone works well in about 40 percent of cases, Dr. Pandya says. “We use 2 percent to 4 percent commercially; 5 percent to 10 percent solutions are frequently compounded by dermatologists. We often enhance penetration with tretinoin and glycolic acid.”

Many hydroquinone products contain sunscreens and antioxidants.

“It’s not clear if these ingredients are necessary,” he says, “but some products that include retinoids and steroids have been shown to be better than hydroquinone alone.”

One popular product contains fluocinolone, hydroquinone 4 percent and tretinoin, he adds. In a 641-patient study, 70 percent of patients who used this cream achieved a 75 percent reduction in melasma (Taylor SC, Torok H, Jones T, et al. Cutis. 2003;72(1):67-72). “The problem is, around 40 percent of patients experienced erythema or desquamation,” he says.

In another study, patients used the cream daily for up to eight weeks, then twice weekly. Only 8 percent of patients experienced irritation because whenever irritation began to appear, patients discontinued the product for a few days, then restarted - applying a moisturizing cream before the triple combination cream (Arellano I, Cestari T, Ocampo-Candiani J, et al. J Eur Acad Dermatol Venereol. 2012;26(5):611-618).

If the triple combination cream fails to improve a patient’s hydroquinone after eight weeks, Dr. Pandya says, “I increase the hydroquinone to 6 percent or 8 percent. If the patient has telangectasias, I reduce the steroid to desonide, hydrocortisone or pimecrolimus. And if the patient develops irritation, I reduce the tretinoin concentration.”

Combining topicals with laser

A recent study combined the triple combination cream with pulsed dye laser, which Dr. Pandya says addresses melasma’s vascular changes. Patients underwent three laser sessions performed three weeks apart, and the combination regimen provided much better results than the cream alone (Passeron T, Fontas E, Kang HY, et al. Arch Dermatol. 2011;147(9):1106-1108). As such, he says, “This approach might be used more commonly in the future.”

Somewhat similarly, “Laser toning is one of the hottest melasma treatments in Southeast Asia,” he says.

In a split-face study, investigators performed five sessions spaced one week apart with the Q-switched 1,064 nm Nd:YAG laser at sub-photothermolytic doses. Twelve weeks post-treatment, patients achieved, on average, 93 percent improvement according to a colorimeter and a 76 percent reduction in Melasma Area and Severity index (MASI) scores (Wattanakrai P, Mornchan R, Eimpunth S. Dermatol Surg. 2010;36(1):76-87).

“Four of 22 patients experienced rebound hyperpigmentation, and four patients had hypopigmentation,” Dr. Pandya says.

Regarding the fractionated 1,927 nm thulium laser, a retrospective report included 20 cases in which patients also got clobetasol and hydroquinone 4 percent one month after laser treatment. At four weeks post-treatment, MASI scores dropped from 13 to eight, and seven of 15 patients reported recurrences. “But only 2 percent experienced PIH (Niwa Massaki AB, Eimpunth S, Fabi SG, et al. Lasers Surg Med. 2013;45(2):95-101),” he says.

An intriguing treatment that’s popular in Asia involves oral or topical tranexamic acid, a plasma inhibitor that can modestly decrease melanin levels in mild-to-moderate melasma without causing adverse events (Na JI, Choi SY, Yang SH, et al. J Eur Acad Dermatol Venereol. 2013;27(8):1035-1039. Wu S, Shi H, Wu H, et al. Aesthetic Plast Surg. 2012;36(4):964-970), Dr. Pandya says.

Next: Getting measurable results from peels

Results from peels

The only peels shown to achieve measurable results for melasma in medical literature involved glycolic acid and modified Kligman’s formula (Sarkar R, Kaur C, Bhalla M, Kanwar AJ. Dermatol Surg. 2002;28(9):828-832), he says.

“You must give modified Kligman’s formula, and six peels performed three weeks apart, and patients will get on average 80 percent improvement after 21 weeks,” versus 63 percent improvement at this time point for modified Kligman’s formula alone, Dr. Pandya says. But he and his colleagues tried to replicate these results in a split-face study with only four peels at a lower concentration and saw no improvement (Hurley ME, Guevara IL, Gonzales RM, Pandya AG. Arch Dermatol. 2002;138(12):1578-1582).

Among oral antioxidants, he says, procyanidin has been shown to improve melasma by an average of 20 percent in a double-blinded, randomized, placebo-controlled trial (Handog EB, Galang DA, de Leon-Godinez MA, Chan GP. Int J Dermatol. 2009;48(8):896-901). But another study showed that polypodium leucotomos produced no effect (Ahmed AM, Lopez I, Perese F, et al. JAMA Dermatol. 2013;149(8):981-983).

Other agents including Chinese herbs, kojic acid and licorice extract appear effective for melasma, according to Dr. Pandya.

“These studies are not very rigorous, but these agents seem to provide some improvement,” he says.

Disclosures: Dr. Pandya is a consultant for Galderma and an investigator for Mary Kay.