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Clinical Updates

Amit G. Pandya, MD

Do Peeling Agents Work for Melasma?

Amit G. Pandya, MD

Wednesday, September 01, 2004

Melasma is one of the most common pigmentary disorders in patients with skin of color, and may also be observed, although less frequently, in Caucasians. Estimates of prevalence range from 1.5% to 10.1%, based on patients presenting to outpatient clinics in various countries.1-6 Despite its high prevalence, treatment of melasma is often difficult, causing frustration for both patients and physicians. Since melasma is exacerbated by sun exposure, sunscreens are critical for successful treatment.

Hydroquinone is the most commonly used depigmenting agent worldwide for melasma. Maximum treatment effect is usually seen within a few months, and one study demonstrated a 40% rate of complete clearing after 12 weeks of therapy with 4% hydroquinone.7 In order to improve efficacy, many agents have been added to hydroquinone, including glycolic acid,8 tretinoin,9 and corticosteroids. A recently developed formulation containing hydroquinone, tretinoin, and fluocinolone acetonide showed significant improvement in 78% of subjects in a large, multicenter trial.10 Despite these successful outcomes, many patients relapse or do not clear completely with topical therapy. Thus, other modalities, including chemical peels, have been used in the treatment of melasma in order to achieve greater success.

Peeling agents are an attractive alternative in the treatment of melasma. Milder peeling agents, such as glycolic acid, remove the stratum corneum, and thus may enhance the penetration of depigmenting agents. Stronger peeling agents, such as trichloracetic acid, remove deeper layers of the epidermis, and may also remove the superficial dermis, including the pigmentation causing melasma. Unfortunately, peeling agents that cause irritation often lead to unacceptable postinflammatory hyperpigmentation, particularly in patients with skin of color. Several studies have evaluated the efficacy of peeling agents for melasma.

Lim et al. studied 10 women from Singapore with melasma treated with glycolic acid.11 The patients applied a cream containing 10% glycolic acid and 2% hydroquinone to both sides of the face, and received glycolic acid peels of 20% to 70% concentration to one side of the face only for up to 5 minutes every 3 weeks. The study duration was 26 weeks, during which time the patients received a total of 8 peels. All patients had at least 4 peels at a 70% concentration. The peeled side did somewhat better, but the difference was not statistically significant, using subjective methods of assessing pigmentation. No instrumentation was used to assess the degree of pigmentation. Stinging and redness lasting less than 1 hour occurred in all patients. One experienced a burn with a 20% glycolic acid peel, causing temporary hyperpigmentation.

Lawrence et al. reported a series of 16 women of various skin types with melasma who were treated with monthly 70% glycolic acid peels on one side of the face and Jessner's peels on the other 12. Fourteen patients received 1 to 3 peels. The average lightening in pigmentation was similar on both sides, and the overall melasma area and severity index (MASI) decreased by 63%, with no difference between the glycolic acid side and the Jessner's side. Unfortunately, all patients also applied tretinoin and hydroquinone to both sides of the face, and there was no control. Evaluation of patient improvement included objective colorimetry, which did not show a difference between the two sides. Most patients found the glycolic acid peel more painful than the Jessner's peel. Three patients had serous crusting and 4 had persistent erythema on the glycolic acid side, requiring parenteral or topical corticosteroids.

A study performed in India on 25 women with moderate-to-severe melasma used 10% glycolic acid and 2% hydroquinone applied daily to the lesions along with monthly 50% glycolic acid peels up to 5 minutes for 3 months.13 The average improvement in MASI score was 46.7%, but there was no control group and the methods of evaluating pigmentation were subjective. Again, the presence of daily hydroquinone therapy causes difficulty in evaluating the true efficacy of the peels in this study. Only 1 patient developed hyperpigmentation after 3 peels, while the others had no side effects.

Another study from India treated 40 patients with melasma using a modified Kligman's formula (tretinoin, hydroquinone, and hydrocortisone) for 21 weeks.14 One half of the patients also received serial glycolic acid peels of 30% to 40% concentration for 1 to 3 minutes at 3-week intervals. The peeled group had an 80% improvement in MASI score, while the nonpeeled group had an improvement of 63%. The difference between the groups was statistically significant, but again, the methods of evaluation were subjective and there was no evaluator-blinding performed. Adverse effects were minimal, with all patients in the peel group and 8 in the control group developing mild erythema and superficial desquamation. Among patients in the peel group, 2 developed focal superficial vesicles with postinflammatory hyperpigmentation, and 2 had persistent erythema, requiring topical corticosteroids.

A small study from Italy reported 20 patients with melasma who were treated with 6 to 12 peels containing 50% glycolic acid and 10% kojic acid at 2-week intervals.15 Using subjective evaluation methods, the investigators found that 30% of the patients had complete regression, 60% had partial regression, and 10% did not improve. However, the patients were of lighter skin types (2 and 3) and there was no control group. Mild desquamation lasting 3 to 4 days was noted in most patients. A small, uncontrolled study including 6 African-American and Hispanic patients with melasma treated with 5 salicylic acid peels of 20% to 30% concentration at 2-week intervals showed moderate-to-significant improvement in 4 patients (66%).16 However, all patients also used daily 4% hydroquinone topically and the methods of evaluation were subjective. Tolerance to the peels was generally good.

A recurrent theme in the above studies is a caution to avoid irritation in patients with skin of color, since this can lead to postinflammatory hyperpigmentation. Indeed, stronger peeling agents, such as trichloracetic acid, are rarely used in darker-skinned patients because of this risk, with all recent studies using milder glycolic, salicylic, and kojic acid peels. Unfortunately, most studies using peeling agents for melasma lack controls, blinding, and objective methods of evaluation, or do not study typically resistant darker skin types.

To address these problems, a study was performed using glycolic acid peels on a uniform group of 21 Hispanic women with melasma who applied 4% hydroquinone twice daily to both sides of the face.17 The patients received glycolic acid peels of 20% to 30% concentration for 3 to 5 minutes to one side of the face only, with the other side serving as a control. The goal was to determine if glycolic acid peels added to a regimen containing daily 4% hydroquinone cream was better than the use of 4% hydroquinone alone. A total of 4 peels were applied, at 2-week intervals. Investigators were blinded, and improvement was objectively assessed using a mexameter (narrow-band reflectance spectrometer). Subjective evaluation was performed using physician and patient global assessments, linear analog scale, and MASI scores. As expected, both sides of the face improved significantly, but there was no added benefit to the side receiving the glycolic acid peels. All patients had mild tingling and erythema during the peel, and only 3 were able to tolerate a peel duration of 5 minutes. Four developed moderate or severe erythema during and after a peel, but without epidermolysis or erosions.

With the conflicting data presented above, the efficacy of peeling agents in the treatment of melasma is anything but clear. Chemical peels remain one of the most commonly performed procedures by dermatologists. These peels are often used in patients with skin of color to improve the appearance of the skin. While texture may improve with the use of peels, there is not good evidence that melasma can be improved. Mild peels tend to be well tolerated, but the therapeutic window is narrow and irritation with resulting postinflammatory hyperpigmentation may occur. The cost of a series of peels may be significant. Thus far, the best results in patients with melasma have been obtained using varying formulations containing hydroquinone, tretinoin, and corticosteroids. Further randomized, controlled trials using peeling agents of various concentrations and formulations are needed before this therapy can be recommended for melasma.

References

  1. Castanon RE, Anderson N. Community dermatology and the management of skin diseases in developing countries. Trop Doctor. 1992;22(suppl 1):3-6.
  2. Arenas R. Melasma. Dermatologia. Atlas, Diagnostico y Tratamiento. Mexico: Interamericana McGraw-Hill; 1996:96-97.
  3. Tomb RR, Nassar JS. Profil des pathologies cutanées observées en clinique dermatologique (1995-2000). J Méd Lib. 2000;48:302-309.
  4. Failmezger C. Incidence of skin disease in Cuzco, Peru. Int J Dermatol. 1992;31:560.
  5. Parthasaradhi A, Al Gufai AF. The pattern of skin disease in Hail region, Saudi Arabia. Ann Saudi Med. 1998;18:558-561.
  6. Hiletework M. Skin diseases seen in Kazanchis health center. Ethiopian Med J. 1998;36:245-253.
  7. Ennes SBP, Paschoalick RC, Mota de Avelar Alchorne M. A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma. J Dermatol Treatment. 2000;11:173-179.
  8. Guevara IL, Pandya AG. Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma. Int J Dermatol. 2003; 42:966-972.
  9. Kligman AM, Willis I. A new formula for depigmenting human skin. Arch Dermatol. 1975;111:40-48.
  10. Taylor SC, Torok H, Jones T, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003; 72:67-72.
  11. Lim JTE, Tham SN. Glycolic acid peels in the treatment of melasma among Asian women. Dermatol Surg. 1997;23:177-179.
  12. Lawrence N, Cox SE, Brody HJ. Treatment of melasma with Jessner's solution versus glycolic acid: A comparison of clinical efficacy and evaluation of the predictive ability of Wood's light examination. J Am Acad Dermatol. 1997;36:589-593.
  13. Javaheri SM, Handa S, Kaur I, Kumar B. Safety and efficacy of glycolic acid facial peel in Indian women with melasma. Int J Dermatol. 2001; 40:354-357.
  14. Sarkar R, Kaur C, Bhalla M, Kanwar AJ. The combination of glycolic acid peels with a topical regimen in the treatment of melasma in dark-skinned patients: A comparative study. Dermatol Surg. 2002;28:828-832.
  15. Cotollessa C, Peris K, Onorati MT, Fargnioli MC, Chiment S. The use of chemical peelings in the treatment of different cutaneous hyperpigmentation. Dermatol Surg. 1999;25:450-454.
  16. Grimes P. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999;25:18-22.
  17. Hurley ME, Guevara IL, Gonzalez RM, Pandya AG. Efficacy of glycolic acid peels in the treatment of melasma. Arch Dermatol. 2002;138:1578-1582.
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