Different therapeutic modalities for treatment of melasma

Authors


Rania M Abdel Hay, MD, 13th Osman Towers, Maadi, Cairo 11431, Egypt. E-mail: omleila2@yahoo.com

Summary

Background  Chemical peels and topical depigmenting agents have become a popular modality in the treatment of melasma.

Aims  To compare the clinical efficacy of trichloroacetic acid peel 20%vs. Jessner’s solution peel vs. the topical mixture of hydroquinone 2% and kojic acid.

Patients and methods  Forty five patients with melasma were randomly assigned into three groups of fifteen patients each. Group A received Jessner’s solution peel, group B received trichloroacetic acid peel 20%, and group C received topical hydroquinone 2% and kojic acid. All patients were seen in follow-up period after 16 weeks; clinical evaluation using Melasma Area and Severity Index (MASI) score and photography were recorded before and after treatment and after 16 weeks.

Results  There was a decrease in MASI score in all three groups after treatment and after follow-up period but after treatment MASI score was statistically significantly lower in group A than group C (P = 0.01), and it was also statistically significantly lower in group B than group C (< 0.001) but there was no statistically significant difference between groups A and B. After the follow-up period, MASI score was statistically significantly lower in group A than group C (< 0.001), statistically significantly lower in group B than group C (P < 0.001), and statistically significantly lower in group B than group A (P = 0.035). The statistical analysis was done through one-way anova followed by least significant difference (LSD).

Conclusion  Trichloroacetic acid 20% showed better results than Jessner’s solution as peeling agent and hydroquinone 2% with kojic acid as a topical agent in the treatment of melasma.

Introduction

Melasma is a disorder of macular hyperpigmentation, often affecting women and mostly involving sun-exposed areas.1 Multiple factors have been postulated in the pathogenesis of melasma.2

There are many modalities of treatment, but the relapse rate is usually high after therapy.1 Several therapeutic modalities either alone or in combination protocols had been studied.3–6 Combination therapies such as hydroquinone, tretinoin, and corticosteroids have been used in the treatment of melasma, and are thought to increase efficacy as compared with monotherapy.4

Chemical peeling is a skin-wounding procedure that can have some potentially undesirable side effects, and tolerance to this procedure may vary from person to person.7

The aim of our study is to compare the efficacy of chemical peeling and topical hypopigmenting agents as different therapeutic modalities for melasma.

Materials and methods

This prospective, randomized study compared the efficacy of three different modalities in the treatment of melasma. The study was approved by the Dermatology Research Ethics Committee Office, Faculty of Medicine, Cairo University. Blinding of the patients was not accessible for ethical purposes. Patient participation in this study consisted of treatment for 6–8 weeks with follow-up visits for 16 weeks. All participants were subjected to full history taking, and a photograph was taken before starting treatment, at the end of treatment, and after the follow-up period. Wood’s light examination was done before treatment to determine the type of melasma (epidermal, dermal or mixed)8 and only patients with dermal type were excluded from the study. The results were evaluated by a blinded clinical investigator by using the Melasma Area and Severity Index (MASI) at baseline and at the end of the peeling sessions (Fig. 1). Patients were randomly divided into three groups: group A and B primed with retinoic acid 0.05% once at night for 2 weeks then peeling was done using Jessner’s solution (group A) or trichloroacetic acid (TCA) 20% (group B) for six sessions with 1 week apart. Group C was given topical hydroquinone 2% and kojic acid 2% (as two separate products applied together at night) to be used for 2 months. All patients were strictly instructed to apply sunscreen 45 SPF daily every 4 h in the morning. The study was conducted in winter.

Figure 1.

 MASI Score Pre-therapy/Post-therapy/F.U. Df, darkness of forehead; Hf, homogenecity of forehead; Af, area of forehead; Dmr, darkness of right malar region; Hmr, homogenecity of right malar region; Amr, area of right malar region; Dml, darkness of left malar region; Hml, homogenecity of left malar region; Aml, area of left malar region; Dc, darkness of chin; Hc, homogenecity of chin; Ac, area of chin.

Using the statistical package (SPSS Inc., Chicago, U.S.), the data were summarized using the mean, standard deviation (SD) and range for quantitative variables and the percentage for qualitative variables. Comparison in between groups was done using Student’s t-test for qualitative variables and anova (analysis of variants) with Post hoc test using least significant difference (LSD) for qualitative variables. P < 0.05 was considered statistically significant.

Results

A total of 60 ambulatory female patients with melasma were enrolled from the dermatology outpatient clinic, Cairo University. Of the 60 patients evaluated, 45 (75%) patients entered and completed the study (Fig. 2). The patients’ ages ranged from 24–50 years with a mean age 34.16 ± 6.76. Relevant clinical findings are illustrated in Table 1. Wood’s light examination showed the same contrast (mixed type of melasma) in 88.88% of patients and increased in the color of the lesion (epidermal nature of melasma) only in 11.11% of patients.

Figure 2.

 Flow-chart of patients participating in the study.

Table 1.   Relevant clinical findings in Groups A, B, and C
  Group AGroup BGroup C
n%n%n%
Fitzpatrick skin typeIII1066.67746.67960
IV533.33853.33640
Pattern of melasmaCentrofacial853.33320853.33
Malar746.671280746.67
Aggravating factorsPregnancy1386.671066.671173.33
Sun exposure1173.3312801066.67
OCPs640426.6726.67
Wood’s lightIncreased213.3316.67213.33
Same1386.671493.331386.67

The MASI score in group A before treatment (mean ± SD = 13.660 ± 4.363) decreased significantly (< 0.001) following treatment (mean ± SD = 5.560 ± 2.637) and at the end of the follow-up period (mean ± SD = 7.647 ± 3.943). In group B, MASI score before treatment (mean ± SD = 12.207 ± 2.987) also decreased significantly (< 0.001) following treatment sessions (mean ± SD = 4.060 ± 1.485) and at the end of the follow-up period (mean ± SD = 5.547 ± 1.454) (Fig. 3a,b,c). In group C, MASI score before treatment (mean ± SD = 14.500 ± 2.107) again decreased significantly (< 0.001) after treatment (mean ± SD = 8.327 ± 2.172) and at the end of the follow-up period (10.813 ± 1.778) (Fig. 4a,b,c).

Figure 3.

 (a) Patient 1 (group B) before treatment, (b) patient 1 (group B) after treatment, (c) patient 1 (group B) after follow-up.

Figure 4.

 (a) Patient 2 (group C) before treatment, (b) patient 2 (group C) after treatment, (c) patient 2 (group C) after follow-up.

Our statistical analysis (using anova test) revealed a significant difference between the three groups after treatment and after the follow-up period (Table 2 and Fig. 5). When these results were statistically analyzed using LSD, MASI score was statistically significantly lower in group A than group C (P = 0.01), and it was also statistically significant lower in group B than group C (P < 0.001) but there was no statistically significant difference between groups A and B. However, there was a significant difference between all the three groups regarding the MASI score after follow up; MASI score was statistically significantly lower in group A than group C (P < 0.001), statistically significantly lower in group B than group C (P < 0.001), and also statistically significantly lower in group B than group A (P = 0.035).

Table 2.   Mean Melasma Area Severity Index (MASI) before treatment, after treatment, and after the follow-up period and significant difference among the groups (using anova test)
MASI (Mean ± SD)Group AGroup BGroup CP-value
  1. *Significant P-value.

  2. Using one-way anova, statistical analysis revealed no significant difference between the three studied groups with regard to MASI score before treatment, P = 0.163 (P-value is significant ≤0.05).

  3. Using one-way anova, statistical analysis revealed there was a significant difference between the three studied groups as regard to MASI score after treatment and after the follow-up period = 0.00 (P-value is significant ≤0.05).

Before treatment13.660 ± 4.36312.207 ± 2.98714.50 ± 2.1070.163
After treatment5.560 ± 2.6374.060 ± 1.4858.327 ± 2.1720.00*
After follow-up period7.647 ± 3.9435.547 ± 1.45410.813 ± 1.7780.00*
Figure 5.

 The mean MASI score over the course of the study in all three groups with most improvement in group B.

In our study, postpeeling erythema developed in 30% of patients in group (A) and 20% of patients in group (B) and it was transient (<2 weeks); discomfort occurred in 25% in both groups. One patient in group A and three patients in group B showed postinflammatory hyperpigmentation as a side effect and it was treated by topical tretinoin.

Discussion

Treatment of melasma still remains challenging due to the prolonged duration of therapy. The substantial relapse rate, which is mainly attributed to persistence of the exacerbating factors (sun exposure) which is inevitable in this part of the world, is still an obstacle.

Quantitative analysis of improvement in melasma is difficult. Mostly, MASI score, developed by Kimbrough-Green et al.,9,10 is used for the assessment.11 Mexameter has been developed to provide objective measurement of melanin.12

Prepeeling preparation with retinoic acid could lead to more quick and uniform infiltration of the peeling solution with decreasing risk of complications.13

Our results revealed that in group A there was a statistically significant decrease (< 0.001) in MASI score after treatment. Although a slight elevation occurred at the end of the follow-up period, there was still a statistically significant decrease (< 0.001). Our results were in agreement with Ejaz et al.9 who reported that Jessner’s solution represented an effective peeling agent.

In group B there was a statistically significant decrease (< 0.001) in MASI score after treatment than before treatment. Similar to group A, the MASI score was slightly elevated at the end of the follow up period. However there was still a statistically significant (< 0.001) decrease. Our results were in accordance with Cotellessa et al.14 and Chun et al.15 who concluded that TCA was effective in the treatment of cutaneous hyperpigmentations.

In group C there was a statistically significant decrease (< 0.001) in MASI score after treatment. Again a slight relapse occurred at the end of the follow up. However, there was still a statistically significant decrease (< 0.001).

Although the drop in the mean MASI score of group C was the least, the increase in the mean MASI score during the follow-up was very close to that of Group B. This implied that the topical therapy used might guarantee very minimal relapse given quite a long period of treatment. Our results were in agreement with other studies4–6,16–18 which revealed the role of different topical medications in the treatment of hyperpigmentation.

Our results suggested that TCA might be superior to Jessner’s solution and topical treatment since it provided more lightening with maintained improvement during the follow-up. However, the difference in improvement of melasma was not so significant when comparing group A and group B after treatment but still there was a significant difference after the follow-up period. This suggested that TCA might give better long-term improvement whereas Jessner’s solution might give impressive and safer short-term improvement since postinflammatory hyperpigmentation observed with Jessner’s solution was less than that seen with TCA.

Our data revealed increased incidence of postinflammatory hyperpigmentation in group B; this could be explained by the presence of more patients with skin phototype IV, who are more prone to postinflammatory hyperpigmentation,19 in this group.

Although topical treatment seemed to be the worst treatment option, it showed very similar relapse to TCA; nevertheless no side effects were reported. Accordingly, we merely suggested possibly more promising results to be encountered with this topical combination, but it needed further investigations and large-scale studies with longer duration of therapy.

Proper patient selection, adequate counseling, and priming the skin in addition to good intra- and postoperative care are essential for satisfactory cosmetic results. Possible side effects of chemical peeling include pigmentary changes, infection, scarring (which is rare in superficial peels), allergic reactions, milia, acneiform eruptions, and persistent erythema for more than 3 weeks.13,20

Finally, we recommend the combination of both Jessner’s solution and TCA, where Jessner’s can be used at first in order to assess the patient’s response, upon which selection of TCA concentration in successive sessions can be determined. Topical depigmenting agents can be a choice in dark-skinned patients with increased susceptibility to hyperpigmentation, but more than 2 months of therapy is required. The combination of chemical peeling with topical preparation can improve the results and maintain the response to therapy.21 Daily use of sunscreens (SPF 50+) and avoidance of precipitating factors should be advised.

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