Strategies to Minimize Irritation and Potential Iatrogenic Post-Inflammatory Pigmentation When Treating Acne Patients With Skin of Color

By Joshua Zeichner MD

INTRODUCTION
Post-inflammatory pigmentation (PIH) is a frequent complication of skin inflammation in patients with skin of color, so it is important to reduce the risk of potential irritation of topical medications when treating acne patients.

When acne lesions resolve in patients with skin of color, they frequently leave behind hyperpigmented macules that can persist for months to years. In fact, PIH may develop after any type of inflammation in the skin.1 While topical acne medications are extremely efficacious, their most common side effects are local cutaneous adverse events, including erythema, peeling, and burning. Medication-induced irritant contact dermatitis can also lead to PIH. This type of pigmentation can have a significant psychosocial impact on affected individuals,2 so it is important to treat acne effectively while minimizing the risk of iatrogenic PIH.

SETTINGS AND METHODS
There are several methods by which irritation from topical acne medications can be minimized. Some pearls for selecting an appropriate treatment regimen for a patient with skin of color are discussed below.

When considering a topical retinoid or a benzoyl peroxide containing product, select ones with lower concentrations of the active ingredient. Clinical trials comparing potential irritancy of tretinoin microsphere 0.04% and 0.1% gels have demonstrated less irritation in the groups using the lower concentration product.3 Similarly, tazarotene 0.05% cream has demonstrated less cutaneous irritation than tazarotene 0.1% cream.4 Moreover, evaluations of benzoyl peroxide at multiple concentrations have demonstrated similar efficacy among 2.5%, 5%, and 10% creams. However, cutaneous adverse events from the 2.5% containing cream were statistically significantly lower than the 10% cream.5

Consensus guidelines for the treatment of acne recommend the use of combination therapy. Multiple medications with different mechanisms of action can effectively address the multiple pathophysiological factors that lead to acne.6 An added benefit of combination therapy is the reduction of potential irritation of topical retinoids from the other products. In a clinical trial comparing the use of adapalene 0.1% gel alone to fixed-dose combination clindamycin 1%/benzoyl peroxide 5% (C 1%/BPO 5%) gel (tube) in the morning and adapalene 0.1% gel in the evening, there was less cutaneous irritation in the combination therapy group. This was attributed to mitigating effects from excipients in the C/BPO product.7 A second study comparing tazarotene 0.1% cream along with CP 1%/BPO 5% gel (tube) in combination with tazarotene 0.1% cream showed similar results. While the difference was not statistically significant, a trend of less peeling was observed in the combination group and was attributed to moisturizing ingredients in the C/BPO product.8 Finally, fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% gel in a vehicle with two humectants has been shown to be a safe treatment in patients with skin of color. In a meta-analysis of three randomized, double-blind studies of over 900 participants, patients with Fitzpatrick skin types IV–VI were no more susceptible to cutaneous irritation than those with Fitzpatrick skin types I–III.9

Topical retinoid therapy monotherapy can be an appropriate treatment for some acne patients, especially those with primarily comedonal disease.6 Moreover, in patients with skin of color, topical retinoids may help improve post-inflammatory pigmentation.10-12 While effective, topical retinoids commonly cause skin erythema, peeling, and dryness, especially during the initial two week retinization period. One way to help minimize these cutaneous side effects is the use of a moisturizer prior to application of the retinoid. A study evaluating the use of tazarotene 0.1% cream alone compared to moisturizing twice daily along with tazarotene 0.1% cream showed statistically significant reduced dryness in the moisturizing group (P<0.01) and a trend towards less erythema and peeling. The evening moisturizer was applied 20 minutes prior to application of tazarotene. Efficacy was equivalent between groups and unaffected by moisturizing prior to application of tazarotene.13

CLINICAL BOTTOM LINE
Minimizing iatrogenic irritation and post-inflammatory pigmentation can be achieved by 1) the use of lowest concentration and least irritating products possible; 2) the use of combination therapy with products with moisturizing vehicles; and 3) the use of moisturizers in combination with topical medications.

DISCLOSURES
Dr. Zeichner has served as an advisory board member, consultant, or investigator for Coria, Galderma, Medicis, Onset Dermatologics, and Ortho Dermatologics.

REFERENCES
1. Davis EC and Callender VD. Postinflammatory Hyperpigmentation: A Review of the Epidemiology, Clinical Features, and Treatment Options in Skin of Color. J Clin Aesthet Dermatol. 2010;3(7):20-31.
2. Chang MW. Disorders of hyperpigmentation. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 2nd ed. Elsevier Mosby; 2009: 333-389.
3. Dosik JS, Homer K, Arsonnaud S. Cumulative irritation potential of adapalene 0.1% cream and gel compared with tretinoin microsphere 0.04% and 0.1%. Cutis. 2005;75(4):238-243.
4. Dosik JS, Homer K, Arsonnaud S. Cumulative irritation potential of adapalene 0.1% cream and gel compared with tazarotene cream 0.05% and 0.1%. Cutis. 2005;75(5):289-293.
5. Mills OH Jr, Kligman AM, Pochi P, Comite H. Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol. 1986;25(10):664-667.
6. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol. 2009;60(suppl 5):1S-50S.
7. Del Rosso JQ. Study results of benzoyl peroxide 5%/Clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris. J Drugs Dermatol. 2007;6(6):616-622.
8. Tanghetti E, Abramovits W, Solomon B, et al. Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: A multicenter, double-blind, randomized parallel-gorup trial. J Drugs Dermatol. 2006;5(3):256-261.
9. Callender VD, Preston N, Osborn C, et al. A Meta-analysis to Investigate the Relation Between Fitzpatrick Skin Types and Tolerability of Adapalene-Benzoyl Peroxide Topical Gel in Subjects with Mild or Moderate Acne. J Clin Aesthet Dermatol. 2010;3(8):15-19.
10. Jacyk WK, Mpofu P. Adapalene gel 0.1% for topical treatment of acne vulgaris in African patients. Cutis. 2001;68(suppl 4):48-54.
11. Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et al. Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. N Engl J Med. 1993;328(20):1438-1443.
12. Grimes P, Callender V. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: A double-blind, randomized, vehicle-controlled study. Cutis. 2006;77(1):45-50.
13. Tanghetti E, et al. Moisturizer use enhances facial tolerability of tazarotene 0.1% cream without compromising efficacy in patients with acne vulgaris. Poster presented at 32nd Annual Hawaii Dermatology Seminar, 2008.

About the author

Joshua Zeichner MD

Mount Sinai Medical Center, New York, NY

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