Tips for Topical Management of Localized Pigmentation

When confronted with complaints of localized pigmentary alterations, first and foremost, it is essential to identify and treat any underlying dermatoses and stress the importance of sun protection. Patients must use sunscreens—preferably containing physical blockers like titanium dioxide or zinc oxide—on all sun-exposed skin on a daily basis. Additionally, patients should practice UV avoidance through the use of physical barriers like hats and clothing that will reduce exposure.

In the case of melasma or PIH, topical treatment options include retinoids, azelaic acid, hydroquinone, chemical peels, and cosmeceuticals. Reassurance and time are also essential elements of the treatment regimen that are sometimes overlooked by the physician and the patient.¹

The selection of a particular retinoid may depend on the preference of the prescriber or patient. Recent research suggests that tazarotene 0.1% cream may offer better efficacy than adapalene 0.3% gel for the management of post-inflammatory hyperpigmentation. Findings come from a controlled, blinded trial involving 180 subjects with PIH related to acne.2 Investigators evaluated improvement of both PIH and acne among subjects, who included African-Americans, Asians, and Hispanics. While 20 percent of patients in the tazarotene 0.1% cream group had complete resolution at week 16, only seven percent of patients in the adapalene 0.3% gel group achieved complete resolution at this point.

Hydroquinone remains a workhorse of melasma management, despite recent controversy. The supervised use of prescription topical hydroquinone had no more than a theoretical risk of malignancy, developing ochronosis, or other long-term safety side effects.³ There is no substantial evidence to prove carcinogenicity. Importantly, unsupervised use of hydroquinone and use of unapproved formulations is reportedly linked to ochronosis and unwanted side effects. Therefore, patient education is crucial. Take time to assure patients of the safety of the prescription agent you recommend—when used as you direct—and describe clearly the intended duration of therapy. Ideally, patients will not fear the use of hydroquinone, but they will have a healthy respect for the agent, reducing the risk for abuse and misuse.

Another topical treatment option is azelaic acid (AzA), which may offer optimal benefit when combined with a topical corticosteroid. In a prospective, single-blinded, right/left comparison study, 40 Indian patients with melasma were instructed to apply AzA cream 20% to one half of the face for 24 weeks and to apply clobetasol 0.05% for eight weeks followed by AzA cream 20% for next 16 weeks. Sequential therapy was associated with more significant improvement than monotherapy (p<0.01).⁴

Triple combination fixed therapy (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) has become a standard intervention, as well, with evidence suggesting that the combination is more effective than hydroquinone monotherapy. In a multicenter randomized control trial of Southeast and East Asian patients (n=260), 129 individuals were assigned to the triple combination group, and 131 were assigned to treatment with hydroquinone alone. During the eight-week study, assessments of Melasma GSS, MASI, and patient satisfaction were made. Triple combination therapy offered superior efficacy to monotherapy in GSS and other variables, although it was associated with more adverse effects.⁵

Numerous case reports and studies have been performed over the last decade highlighting the use of products such as zinc, arbutin, kojic acid, vitamin C based compounds, and green tea extracts, as newer therapies for treating our melasma patients. One example of a novel therapy for melasma that has recently appeared in the literature demonstrates the effects of topical methimazole.⁶ Topical methimazole is a potent peroxidase inhibitor under investigation for the management of hyperpigmentation. Peroxidase is important in the final steps of melanogenesis and in some tyrosinase free cells. Even at high concentrations, methimazole is not melanocytotoxic. Kasraee, et al. showed 20 patients with no TSH, free thyroxine, or free iodothyronine levels. The drug is odorless and very well tolerated. Though more randomized, controlled large cohort trials are needed to further elucidate the role of products such as methimazole, zinc, arbutin, and others, these recent studies give some hope to our patients suffering from melasma for more novel therapies in our armamentarium against this often devastating condition.

Procedures

Superficial chemical peels are generally effective for the management of PIH and melasma when properly applied. Standard options include glycolic acid 20-70%, salicylic acid 20-30%, TCA 10-25%, or Jessner's solution. Pre-treatment with a course of hydroquinone 4% topically (if available) is thought to improve outcomes. Any patient using topical retinoids should discontinue their use for seven days prior to the peel. They may continue to use a non-comedogenic, SPF moisturizer.

Support for the use of glycolic acid peels comes from a study that involved 19 subjects randomized to apply a twicedaily regimen of 2% hydroquinone/10% glycolic acid gel, along with tretinoin 0.05% cream nightly or to undergo six consecutive glycolic acid peels (up to 68%) with no additional topical therapy. Overall, patients treated with peels alone showed a trend for more rapid and greater improvement.⁷

Salicylic acid peels have been shown useful in PIH, including for patients with darker skin types. In an open-label trial, 25 patients were treated with five salicylic acid peels (20- 30% concentration) provided at two-week intervals. Patients underwent two weeks of pre-treatment with hydroquinone 4%. Four of five patients with Fitzpatrick type V or VI had greater than 75 percent improvement in pigmentation.⁸

Laser therapy can be effective for hyperpigmentation with durable improvement, and may be used with topical medications, like tretinoin, or vitamin C.

Seemal R. Desai, MD is on staff at University of Texas Southwestern Medical Center and in private practice in Plano, TX.

Adapted from an article appearing in Practical Dermatology. To read more, including further discussion of device-based treatments, visit: http://bmctoday.net/practicaldermatology/ 2013/06/article.asp?f=management-options-forhyperpigmentation- an-update

1. Taylor S, Grimes P, Lim J,et al. Postinflammatory hyperpigmentation. J Cutan Med Surg. 2009 Jul-Aug;13(4):183-91.
2. Tanghetti E, Dhawan S, Green L, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. J Drugs Dermatol. 2010 May;9(5):549-58.
3. Nordlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone. J Eur Acad Dermatol Venereol. 2006 Aug;20(7):781-7.
4. Sarkar R, Bhalla M, Kanwar AJ. A comparative study of 20% azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark-skinned patients. Dermatology. 2002;205(3):249-54.
5. Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008 Sep;159(3):697-703.
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7. Burns RL, Prevost-Blank PL, Lawry MA, et al. Glycolic acid peels for postinflammatory hyperpigmentation in black patients. A comparative study. Dermatol Surg. 1997 Mar;23(3):171-4.
8. Grimes PE. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999; 25(1):18-22.
9. Kauvar AN. Successful treatment of melasma using a combination of microdermabrasion and Q-switched Nd:YAG lasers. Lasers Surg Med. 2012 Feb;44(2):117-24.
10. Rendon M, Berneburg M, Arellano I, Picardo M. Treatment of melasma. J Am Acad Dermatol 2006;54: S272-81
11. Relyveld GN, Menke HE, Westerhof W. Progressive macular hypomelanosis: an overview. Am J Clin Dermatol. 2007;8(1):13-9. http://www.afterglowskincare.ca/concerns/melasma.php
12. Dr Linda Martin, MBBS (UNSW) Hons 1, Research Fellow, Department of Dermatology, St George Hospital, Sydney, NSW; Associate Professor Dedee Murrell, FAAD, Head of Dermatology, St George Hospital; Dr Richard Wittal, FACD, and Dr John Le Guay, FACD, both from the Vitiligo Clinic, Skin and Cancer Foundation, Darlinghurst, Sydney, NSW. http://www. thevictoriancosmeticinstitute.com.au/skin-pigmentation-treatment/