Retinoids and Azelaic Acid to Treat Acne and Hyperpigmentation in Skin of Color

Long used in the treatment of acne, retinoids offer dermatologists another option for the treatment of hyperpigmentation. The use of retinoids in hyperpigmentation is supported by an increasing body of literature (Table 1). In the current study, tretinoin, tazarotene, and adapalene (ADA), which have been successfully used to treat acne, are reviewed and their effectiveness in hyperpigmentation is discussed.

In a blinded, vehicle-controlled trial, 74 acne patients from darker racial ethnic groups (Fitzpatrick skin types IV to VI) were treated with once-daily application of tazarotene 0.1% cream. The primary efficacy variable was the overall disease severity of postinflammatory hyperpigmentation (PIH). Patients also were evaluated for the pigmentary intensity of hyperpigmented lesions, area of hyperpigmented lesions, and degree of hypopigmentation.¹ In addition, the tolerability of the medication was evaluated as measured by erythema, burning, peeling, and dryness. These categories had a grading scale of 0 to 5, based on severity.¹ Results showed clinically significant reductions in overall PIH severity and in the intensity and extent of hyperpigmentation when compared with vehicle within 18 weeks (P≤.05).¹ In addition, throughout the study, dryness, erythema, burning, and peeling were mild in both groups.¹

A meta-analysis of 5 randomized trials assessing ADA 0.1% gel evaluated the primary efficacy parameters of total lesion counts (sum of inflammatory and noninflammatory lesions), inflammatory lesion counts, and noninflammatory lesion counts on both Caucasian and African American patients.² The primary safety parameters evaluated were erythema, scaling, and dryness. Each of these adverse events was evaluated on a 0 to 3-point grading scale, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.2 The meta-analyses were compared using the Cochran–Mantel–Haenszel test. Results showed ADA 0.1% gel significantly reduced a greater number of inflammatory lesions among African American patients with Fitzpatrick skin types IV through VI vs Caucasian patients (P=.012).² Reductions in total lesion counts were similar in the 2 groups (P>.3). In addition, there was significantly less erythema (P<.001) and scaling (P=.026) in the African American group.² Although the incidence of dryness was similar for both groups, fewer of the African American subjects had moderate or severe scores for dryness (7% vs 18% of Caucasian). In summary, based on these studies, ADA may have better efficacy for inflammatory lesions in African Americans than in Caucasians and is a good choice for patients with skin of color.²

An open-label trial of 44 black South African patients studied the effects of ADA 0.1% gel on acne and PIH. Investigators observed color change over 12 weeks. Other efficacy variables assessed were inflammatory lesion counts, noninflammatory lesion counts, and overall severity scores.³ The authors noted a reduction in hyperpigmented macules in 66% of patients and a drop in mean total facial lesion count of up to 72%.³

A retrospective meta-analysis combined 3 randomized, double-blind, vehicle-controlled clinical trials using ADA and benzoyl peroxide (BPO) to assess tolerability in skin of color. The study included 909 patients treated over a 12-week period. Patients were evaluated at each visit for erythema, scaling, dryness, and burning, and a score of 0 (none) to 3 (severe) was assigned.⁴ For the meta-analysis, comparisons were made