Developments in topical retinoid therapy for acne

Abstract

Topical retinoic acid was introduced for acne treatment three decades ago. Since that time, researchers have discovered thousands of retinoids, originally defined as chemical analogs of vitamin A. After the identification of nuclear retinoid receptors in 1987, the definition of this class expanded to include molecules that bind to and activate such receptors. The receptor-selective retinoid agents, adapalene and tazarotene, were developed in the 1990s. Other innovations of the past decade include retinoid formulations and methods aimed at limiting retinoid absorption. Cutaneous irritation may be reduced without losing retinoid efficacy by inhibiting retinoid penetration into the deep epidermis and dermis. Examples include tretinoin in slow-release vehicles and the short-contact method of tazarotene gel therapy. Only trace amounts of adapalene are absorbed after topical application, perhaps explaining its relatively low irritancy. New formulations of existing agents, such as additional concentrations of tretinoin in microsphere gel and cream formulations of tazarotene, are now under investigation for acne. Current research focused on receptor selectivity holds the promise of yielding new retinoid molecules with improved benefits and safety.

Successful Treatment of Acne Vulgaris Using a New Method

“…There were no withdrawals due to treatment-related adverse effects because the study protocol allowed patients to adjust the contact period within well-defined limits to avoid such effects. In the previous experience of Bershad,19 tazarotene sensitivity differed substantially among individual patients, an observation supported herein. Data from patients' diary records at week 12 suggest that approximately half of all patients using active treatment had contact times of 3.5 minutes or less, whereas the remainder tolerated longer contact periods (Table 2).…”

“…early experience with tazarotene for facial acne, several patients noted skin discomfort within 10 minutes of application. 19 In some cases, typical retinoid-induced skin irritation occurred, even when tazarotene was removed after such limited exposure. The possibility of avoiding adverse effects by shortening the period of skin contact with tazarotene was intriguing.…”

“…Preliminary exploration suggested that acne improvement and good tolerability might result from exposure times shorter than 5 minutes repeated regularly for 12 weeks. 19 The goal of this study was to assess acne progress and local skin irritation, using a novel short-contact method of applying 0.1% tazarotene gel (Tazorac; Allergan Inc, Irvine, Calif ), in patients with mild to moderate facial acne. Comparisons of these measures were made among 3 groups: those using 0.1% tazarotene gel twice daily (T+T), those using 0.1% tazarotene gel once daily and nonmedicated (vehicle) gel once daily (T +V), and a control group using vehicle gel twice daily (V+V).…”

‘Keratolytic’ Properties of Benzoyl Peroxide and Retinoic Acid Resemble Salicylic Acid in Man

“…This could imply that the action of RA is more time-dependent than the other treatments, perhaps based on its well-documented interaction with nuclear receptors to alter gene transcription in addition to its basic keratolytic properties [1,2,22,23] .…”

Transglutaminases: Nature’s biological glues

“…A recent alternative and useful approach is to modulate endogenous tTgase expression, rather than to administer purified enzyme, by means of specific inducers such as the retinoids. This approach is now a recognized strategy in dermatological conditions such as acne [207], and, as stated above, in the therapy of selected malignancies in i o [196,208]. Although studies are still at the experimental stage, additional encouraging results have been obtained in some animal tumours, e.g.…”