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Topical retinoid therapy is widely accepted as the foundation of successful acne vulgaris therapy. While commonly combined with other topical and systemic treatments, topical retinoid agents are unique in their action on epithelial differentiation, a fundamental and likely primary component of acne pathogenesis. In addition, their anti-inflammatory effects are becoming better appreciated and characterized.
Retinoid agents used for acne include tretinoin and isotretinoin, tazarotene and adapalene. They were developed to maximize vitamin A-like epithelial differentiation activity while minimizing the adverse effects. Firstgeneration retinoids, such as tretinoin (topical) and isotretinoin (systemic), have been used for several decades and have proven invaluable as acne therapy. Third-generation compounds, such as tazarotene and adapalene, are newer retinoids, both with topical once-daily application. Adapalene has become widely used due to its comparable efficacy and favorable tolerability profile when compared with other topical retinoids.
Adapalene in the treatment of acne vulgaris
Adapalene is a naphthoic acid derivative with retinoid action that affects keratinocyte differentiation. The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. Adapalene has demonstrated in vitro specificity for retinoic acid receptor (RAR)-γ, a RAR important in the differentiation of keratinocytes. Adapalene binds tightly to RAR and this composite interacts with another receptor molecule, retinoic X receptor (RXR). The complex of RAR, adapalene and RXR then binds specific sites of DNA. This leads to changes in protein synthesis that affect cell proliferation and differentiation [1]. One study compared the inhibitory effect of adapalene and tretinoin on cultured human keratinocytes by measuring keratinocyte transglutaminase expression, a marker for keratinocyte differentiation. Adapalene showed a tenfold greater inhibition of keratinocyte transglutaminase expression than tretinoin, suggesting stonger in vitro inhibition of keratinocyte dif-ferentiation [2].
Keratinocyte differentiation is important in acne because keratinocyte hyperproliferation is thought to be one of the major pathogenic processes driving the development of microcomedones, the inciting acne lesion [1]. By inhibiting this hyperproliferation, retinoids such as adapalene are considered to be comedolytic. To prove in vivo comedone reduction, a study used the rhino mouse to examine comedone counts after treatment with adapalene cream 0.1%, adapalene gel 0.1% and tretinoin gel 0.025%. All active treatment groups yielded comedone count reductions between 50 and 60% compared with vehicle [3].
Another important aspect of acne pathogenesis is the inflammatory response to comedones, and...