Hyperpigmentation: An Overview of the Common Afflictions

Kimberly A. Cayce; Amy J. McMichael; Steven R. Feldman


Dermatology Nursing. 2004;16(5) 

In This Article

Melasma Therapy

The goal of melasma therapy is to promote degradation of melanosomes, inhibit formation of melanosomes, and retard proliferation of melanocytes (Pandya & Guevara, 2000). Although not a cure in and of itself, one of the most important interventions in managing melasma is the routine use of sunscreens with both UVA and UVB protection. As mentioned previously, epidermal and dermal melasma respond very differently to treatment. Coverup with opaque cosmetics remains essentially the only option for dermal melasma. An exception to this was reported in a pilot study of pulsed CO2 laser followed by Q-switched alexandrite laser that showed promising results (Nouri, Bowes, Chartier, Romagosa, & Spencer, 1999). Multiple therapies are available in the management of epidermal melasma.

Topical agents for melasma include phenols (hydroquinone), retinoids (tretinoin), alpha-hydroxy acids (glycolic acid), salicylic acid, azelaic acid, and kojic acid. The usefulness of hydroquinone as a depigmenting agent has been apparent for years. Efficacy reports range from 64% to 88% (Fitzpatrick, Arndt, el Mofty, & Pathak, 1966; Sanchez & Vazquez, 1982). Hydroquinone works by inhibiting the tyrosinase enzyme, thereby preventing the conversion of dopa to melanin. Most dermatologists recommend hydroquinone 4%, which is prescription strength, but infrequently a higher strength can be compounded. Some authors suggest continuation of low-dose, over-the-counter 2% hydroquinone for maintenance therapy after an initial treatment period (Pathak, Fitzpatrick, & Kraus, 1986). The lengthy time required for satisfactory improvement of melasma with hydroquinone treatment, typically at least 6 months, is frustrating for patients and health care providers. Potential side effects include irritant and allergic contact dermatitis, nail discoloration, and postinflammatory hyper or hypopigmentation (Grimes, 1993). Although uncommon, ochronosis (a permanent, reticulated, ripple-like, sooty pigmentation) can occur, generally with prolonged use of high-concentration hydroquinone (Grimes, 1995).

Tretinoin 0.1% improves melasma, but these advancements generally take time (24 weeks or more) (Griffiths et al., 1993; Kimbrough-Green et al., 1994; Tadaki et al., 1993). Reduction of pigmentation transpires as a result of the retinoid-induced dispersion of keratinocyte pigment granules, its interference with pigment transfer, and acceleration of epidermal turnover (Kligman & Willis, 1975). Adverse effects include erythema, peeling, and possible postinflammatory hyperpigmentation (Grimes, 1995).

Azelaic acid has also been used with some success. This chemical inhibits DNA synthesis in melanocytes and has a modest antityrosinase effect (Ortonne et al., 2003). Comparisons of azelaic acid to 2% hydroquinone revealed superiority with azelaic acid, but no significant difference from 4% hydroquinone (Balina & Graupe, 1991; Verallo-Rowell, Verallo, Graupe, Lopez-Villafuerte, & Garcia-Lopez, 1989). Pruritus, mild transient erythema, scaling, and burning may occur (Fitton & Goa, 1991). Kojic acid is not any more efficacious than other therapies and may trigger more irritation. However, this agent may be effective if a patient has difficulty tolerating other first-line agents.

Combination therapy is more effective than single agents used alone. The mixture of tretinoin 0.1%, hydroquinone 5%, and dexamethasone 0.1% yielded better results than any of the medications alone, and several adaptations of this regimen have since proved useful (Gano & Garcia, 1979; Kang, Chun, & Lee, 1998; Kligman & Willis, 1975). In a population of 641 patients with melasma, a recent trial comparing a triple combination of tretinoin 0.05%, hydroquinone 4%, and fluocinolone acetonide 0.01% proved better than any of the dual combinations of the above agents (Taylor et al., 2003). In addition, clinically significant improvement with the triple therapy was noted as early as 4 weeks with maximum results at 8 weeks (Taylor et al., 2003). Patients should be instructed to apply this combination treatment once daily for a total of 2 to 3 months. To help avoid blotchiness, the medication should cover the entire affected area. The most common adverse event is local irritation, which is generally mild. New, long-term safety trials, involving over 400 patients with melasma, have proven this triple therapy to remain safe even with 6 and 12 months of use (Torok, Jones, Rich, Smith, & Tschen, 2003). The addition of tretinoin to topical steroids increases the epidermal skin thickness (McMichael et al., 1996) which may help explain the maintained safety of this drug. If local irritation does occur, a drug holiday for 1 to 2 days is appropriate.

Others have had success with just the combination of lower-concentration hydroquinone 2% and tretinoin 0.5% (Pathak et al., 1986). One study demonstrated a more rapid response (3 months vs. 10 months) with the addition of chemical peels to a tretinoin/hydroquinone regimen (Lawrence, Cox, & Brody, 1997).

Superficial and medium-depth peels with trichloroacetic acid (TCA), glycolic acid, and salicylic acid benefit some individuals. The addition of glycolic acid peels to a modified Kligman's formula displayed more rapid and greater improvement than the topical regimen alone in one clinical trial (Sarkar, Kaur, Bhalla, & Kanwar, 2002). However, peels must be used with caution in darker-pigmented persons because of the greater risks of postinflammatory hyperpigmention. The association of hypo and hyperpigmentation, scarring, and keloid formation decreased the utilization of deep peels for melasma, especially in dark-complexioned patients (Pandya & Guevara, 2000). Other potential side effects of the chemical peels include atrophy, bacterial and viral infections, milia, telangiectasias, and pore enlargement (Moy, Murad, & Moy, 1993). Dermabrasion is another technique exercised in the management of melasma, but again the increased risk of postinflammatory hyperpigmentation in dark-skinned individuals makes this option less desirable.

Therapy with various lasers including erbium yttrium-aluminum-garnet (er:YAG), Q-switched ruby, dye (510 nm), argon, and neodymium (Nd):YAG lasers have been attempted, but most demonstrate limited if any success in treating melasma. The er:YAG laser revealed some improvement, but significant postinflammatory pigmentation requiring 6 months of treatment resulted (Manaloto & Alster, 1999). Goldberg (1993) and McBurney (1993) demonstrated encouraging responses with the Q-switched ruby laser and the argon laser, but these results were short-lived. Complications included atrophy, hypertrophic scarring, and hypo and hyperpigmentation (Grimes, 1995).