PracticalDermatology

A majority of patients with mild-to-moderate acne will be managed quite adequately with topical therapy alone. We know there are four main pathogenic factors in acne:

• Increased androgen secretion
• Increased sebum production
• P. acnes proliferation
• Faulty keratinization.

Currently, no topical therapy is available to modulate androgen levels or androgen receptors at the follicular level, nor are there topical therapies that can modulate sebum production. However, topical therapies are available to:

• Regulate keratinization
• Decrease P. acnes colonization
• Inhibit associated inflammation.

Topical retinoids primarily function to regulate hyperkeratinization, preventing the formation of microcomedones and encouraging resolution of clinically apparent comedones. They also confer antiinflammatory effects (i.e., reducing and preventing erythematous papules and pustules).^1-5 Despite treatment guidelines indicating that topical retinoids— tretinoin, adapalene, tazarotene (See table)—are appropriate for use in a majority of patients with mild-tomoderate acne,^6,7 data suggest topical retinoids may be underutilized.^8,9

Several topical antibacterials and antimicrobials have been shown to decrease or eradicate P. acnes. Topical benzoyl peroxide has demonstrated activity against P. acnes, and has the benefit of not being associated with promoting antibacterial resistance. Concentration-dependent irritation has been noted, however, data show that 2.5% and 5% concentrations confer similar efficacy to 10% benzoyl peroxide.¹⁰ Benzoyl peroxide is also shown to confer comedolytic and keratolytic effects.¹¹

Topical antibiotics (clindamycin or erythromycin) also confer activity against P. acnes and have demonstrated anti-inflammatory effects.¹² Their use as monotherapy has largely diminished given the substantial body of data showing that use of benzoyl peroxide in combination with a topical antibiotic confers greater efficacy, enhances tolerability compared to either agent alone, and obviates concerns about developing resistance.¹¹

Several fixed-combination formulations are available that feature benzoyl peroxide along with clindamycin. A novel combination of benzoyl peroxide and adapalene is available for once-daily use in the management of acne vulgaris. In trials, adapalene/benzoyl peroxide fixed-dose combination gel was more effective than either component as monotherapy, with safety similar to that of each component and vehicle.¹³

Topical dapsone, a relative newcomer to the market, is the first primarily anti-inflammatory topical treatment for acne. Analysis of pooled data from three studies involving 1,306 patients age 12 to 15 found that dapsone gel was safe and effective when used for up to 12 months.¹⁴

Optimal treatment of acne depends on the initiation of therapy aimed at multiple pathogenic features of the disease, and the majority of patients with mild-to-moderate acne are best treated with a combination of topical therapies. ^6,7,15 Given the importance of topical retinoids in the management of acne and their ability to prevent the formation of the early microcomedo, most patients should be started on a topical retinoid each evening. Treatment is optimized with the addition of a topical antimicrobial, either topical benzoyl peroxide or benzoyl peroxide/ antibiotic combination, each morning. In the case of fixed combination adapalene/benzoyl peroxide, it is indicated for once-daily application.

1. Mills OH Jr, Kligman AM. Assay of comedolytic activity in acne patients. Acta Derm Venereol. 1983;63(1):68-71.
2. Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol. 2008;9(6):369-81.
3. Thielitz A, Krautheim A, Gollnick H. Update in retinoid therapy of acne. Dermatol Ther. 2006 Sep- Oct;19(5):272-9.
4. Shalita A. The integral role of topical and oral retinoids in the early treatment of acne. J Eur Acad Dermatol Venereol. 2001;15 Suppl 3:43-9.
5. Millikan LE. The rationale for using a topical retinoid for inflammatory acne. Am J Clin Dermatol. 2003;4(2):75-80.
6. Thiboutot D, Gollnick H, Bettoli V, et al; Global Alliance to Improve Outcomes in Acne. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol. 2009 May;60(5 Suppl):S1-50.
7. Ghali F, Kang S, Leyden J, Shalita AR, Thiboutot DM. Changing the face of acne therapy. Cutis. 2009 Feb;83(2 Suppl):4-15.
8. Balkrishnan R, Bhosle MJ, Camacho F, Fleischer AB, Feldman SR. Prescribing patterns for topical retinoids: analyses of 15 years of data from the national ambulatory medical care survey. J Dermatolog Treat. 2010 May;21(3):193-200.
9. Balkrishnan R, Fleischer AB Jr, Paruthi S, Feldman SR. Physicians underutilize topical retinoids in the management of acne vulgaris: analysis of U.S. National Practice Data. J Dermatolog Treat. 2003 Sep;14(3):172-6.
10. Sagransky M, Yentzer BA, Feldman SR. Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris. Expert Opin Pharmacother. 2009 Oct;10(15):2555-62.
11. Tanghetti EA, Popp KF. A current review of topical benzoyl peroxide: new perspectives on formulation and utilization. Dermatol Clin. 2009 Jan;27(1):17-24.
12. Del Rosso JQ, Schmidt NF. A review of the anti-inflammatory properties of clindamycin in the treatment of acne vulgaris. Cutis. 2010 Jan;85(1):15-24.
13. Gold LS, Tan J, Cruz-Santana A, et al; Adapalene-BPO Study Group. A North American study of adapalene-benzoyl peroxide combination gel in the treatment of acne. Cutis. 2009 Aug;84(2):110-6.
14. Raimer S, Maloney JM, Bourcier M, et al; United States/Canada Dapsone Gel Study Group. Efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. Cutis. 2008 Feb;81(2):171-8.
15. Krakowski AC, Stendardo S, Eichenfield LF. Practical considerations in acne treatment and the clinical impact of topical combination therapy. Pediatr Dermatol. 2008 Jun;25 Suppl 1:1-14.