percent reduction in epidermal melanin content in skin lesions of the tretinoin group compared to three percent with vehicle. Fifty percent of the subjects treated with tretinoin reported moderate-to-severe erythema and desquamation.11 This trial is one of the best in terms of documentation, photography and inclusion of varying severity of PIH.
Another trial studied once daily applied tazarotene 0.1% cream compared to vehicle in 74 subjects of darker racial groups with PIH. After 18 weeks, the treatment group was shown to be significantly
more effective than vehicle against PIH, achieving greater reductions in intensity and area of hyperpigmentation. On average, evidence of irritation was no more than trace, and dryness no more than mild, in both groups throughout the study.12
The efficacy of clindamycin 1%-benzoyl peroxide (BPO) 5% topical
gel in combination with either tretinoin 0.04% microsphere gel or adapalene 0.1% gel in 167 subjects with pigmented skins for the treatment of acne and PIH was investigated in a recent trial.
Results showed more rapid and greater resolution of PIH from baseline in subjects receiving clindamycin 1%/BPO 5%/tretinoin 0.04% microsphere gel. It was concluded that this finding may indicate that this lower concentration of tretinoin microspere gel causes less irritation and a decreased capability of producing treatment-induced hyperpigmentation in darker skin types.13
The treatment of dermal PIH is more challenging. The histological
features of biopsies obtained from 10 Japanese subjects with various types of hyperpigmented skin lesions found that tretinoin gel (0.1%, 0.2% and 0.4%) along with 5% hydroquinone ointment was histologically effective in reducing epidermal, but not dermal melanosis.14 Accordingly, lesions with primarily dermal hyperpigmentation demonstrated the least amount of clinical improvement.
In summary, formulations of tretinoin, adapalene and tazarotene
have all shown efficacy in treating epidermal causes of PIH, with tretinoin 0.004% microsphere gel probably the least irritating in pigmented skins.
Melasma is an acquired hypermelanosis of unknown etiology characterized by epidermal, dermal, or mixed histological types of hyperpigmentation.9 While the disease may affect all racial groups, it is most frequently observed in women of darker complexion,
especially Latinos and Asians.15
A number of studies have explored the efficacy of topical retinoids as monotherapy in treatment of melasma. A trial consisting of 28 black subjects with melasma compared the efficacy
and tolerability of tretinoin 0.1% cream daily to vehicle cream. After 40 weeks, the tretinoin group demonstrated a 32 percent improvement in the Melasma Area and Severity Index (MASI) score compared with a 10 percent improvement in the vehicle group. Tretinoin was also found to be superior based on colorimetric and histologic analyses. A mild dermatitis was noted to occur in 67 percent of subjects treated with tretinoin.16
Combination therapies, most frequently consisting of hydroquinone,
tretinoin and a topical steroid are thought to be superior to monotherapy in the overall management of melasma.
Not only does tretinoin facilitate the epidermal penetration of hydroquinone, but the incorporation of a topical corticosteroid
helps to reduce the irritative effects of retinoids and hydroquinone.9 Kligman and Willis reported the original triple combination formula effective in the treatment of melasma, which consisted of 5% hydroquinone, 0.1% tretinoin and 0.1% dexamethasone.17 Despite its success, the fact that it contained a fluorinated corticosteroid and a high concentration of tretinoin
made this formula less favorable.8
The first and only triple combination formula to be approved by the Food and Drug Administration (FDA) for the treatment of melasma contains hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01%. This medication should not be used for durations longer than eight weeks due to the potential side effects associated with long-term topical corticosteroids, especially when used on the face.48 The efficacy and safety of this modified triple combination cream for the treatment of melasma
was reported in an eight week study of 1,290 subjects with Fitzpatrick skin types I through VI and moderate-to-severe melasma. The mean MASI score in the study population decreased
significantly at weeks 4 and 8 compared with baseline across all Fitzpatrick skin types. Based on investigators' global assessments, 75 percent of subjects had moderate to complete resolution after eight weeks of treatment. Twenty-seven percent
of subjects experienced at least one adverse effect, mostly due to skin irritation, erythema, or dry skin.18
An eight week trial compared once daily applied triple combination
cream to twice daily applied hydroquinone 4% cream in 120 Latino subjects with moderate-to-severe melasma. At