Harnessing the Anti-inflammatory Effects of Topical Dapsone for Management of Acne
June 2010 | Volume 9 | Issue 6 | Original Article | 667 | Copyright © 2010
Leon H. Kircik, MD
Mount Sinai Medical Center, New York, NY; Indiana University School of Medicine, Indianapolis, IN
Data continue to establish the role of inflammation, not only in the pathogenesis of acne but also in the development of its most devastating sequelum, scarring. Although topical therapy is preferred by most acne patients and the physicians who treat them, historically no topical intervention has provided primarily anti-inflammatory effects. Topical dapsone 5% gel offers documented efficacy for the reduction of both inflammatory and non-inflammatory acne lesions. It has been proven safe, presenting none of the hematologic risks associated with oral dapsone. Data suggest the vehicle formulation enhances healing and contributes to tolerability, making topical dapsone 5% gel a worthwhile anti-inflammatory treatment for many patients with mild-to-moderate acne vulgaris.
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Although acne is one of the most common skin disorders, its pathogenesis is not clearly understood. Propionibacterium acnes (P. acnes) is a commensal organism that plays an active role in acne vulgaris. P. acnes thrives in the presence of excess sebum and has been shown to mediate inflammatory processes at the site of the sebaceous follicle, contributing to the formation of free radical species and generating pro-inflammatory cytokines.1 Coupled with faulty keratinization, excess sebum production and P. acnes colonization contribute to the formation of microcomedones, ultimately leading to development of the comedones, papules, pustules and cysts characteristic of acne.
While the appearance of active acne vulgaris can have a significant impact on a person’s appearance and can be associated with potential physical discomfort, the scarring following acne is the most devastating sequelum to the patient. A better understanding of the pathophysiology of acne and associated scarring has been gained with the most recent in vivo research by Kang et al.2 They reported a marked increase in inflammatory cytokine gene transcripts in active acne lesions, including TNF-α and IL-1b. Importantly, these pro-inflammatory cytokines amplify NF-kB signaling pathways that originally led to their production while also stimulating nearby cells, according to the authors. This investigation also identified significant increases in IL-8 and IL-10. In addition to NF-kB, Activator Protein-1 (AP)-1 is also elevated in acne lesions, leading to elevated matrix metalloproteinases, which degrade collagen—up to 2.5-fold compared to normal skin. Furthermore, the authors note that the inflammatory process is localized to the pilosebaceous unit.2
The most common sequelum of inflammatory acne is scarring, which is devastating to patients. The best way to prevent scarring is, of course, to prevent and treat inflammatory lesions as early as possible. Also, any agent blocking (AP)-1, which increases matrix metalloproteinases that cause scarring via collagen degradation, will be useful in scar prevention.
Topical treatment options for acne include retinoids, antimicrobials, such as erythromycin and clindamycin, and benzoyl peroxide (BPO). Different combination formulations of retinoids, antibiotics and BPO are also available. Topical retinoids primarily act to normalize hyperkeratinization and have been suggested to confer mild anti-inflammatory effects. Topical antimicrobials and benzoyl peroxide target P. acnes, diminishing colonization. Topical antimicrobials may also confer antiinflammatory effects.
Despite the well-known and recently re-affirmed role of inflammation in acne, no primarily anti-inflammatory topical therapy has been available for acne. Anti-inflammatory topical dapsone 5% gel (Aczone Gel 5%, Allergan, Irvine, CA) is now available for topical treatment of acne.
Mechanisms of Action
Although dapsone has proven to be a very powerful treatment in several neutrophilic dermatoses (such as dermatitis herpetiformis) through its anti-inflammatory effects, the mechanism of action of this effect is not well understood. There are several in vitro studies that show the anti-inflammatory effect of dapsone. The successful use of oral dapsone in several sub-epidermal blistering diseases is associated with anti-inflammatory effects by the suppression of neutrophil and eosinophil functions. This effect was demonstrated through dapsone’s inhibition of IL-8 release in cultured human keratinocytes.3
It also has been shown that dapsone suppressed leukocyte integrin function, thus inhibiting migration of neutrophils to extravascular sites.4 Further, in vitro studies by Debol et al. show that dapsone inhibits chemoattractant-induced G-protein activation and suppresses the subsequent signal transduction cascade.5