Acne Treatment

Most cases of acne can benefit from treatment with topical retinoids, and they are considered a cornerstone of acne therapy. They are also the preferred agents for maintenance therapy. The US Food and Drug Administration (FDA) have approved three topical retinoids in the United States: tretinoin, adapalene, and tazarotene (Table). Topical isotretinoin is available in Canada and Europe, but in the United States, only the oral form is approved.

Topical retinoids improve acne by increasing the turnover of follicular epithelial cells, thus normalizing follicular keratinization and inhibiting the development of the precursor acne lesion, the microcomedo. Topical retinoids also help resolve mature comedones, and are now recognized to have direct anti-inflammatory effects as well. Thus, topical retinoids are effective in both comedonal and inflammatory acne. It is also now believed that the application of topical retinoids enhances the penetration of other medications, such as topical antibiotics and benzoyl peroxide.

The first topical retinoid was tretinoin, which became available in 1971. It was initially formulated in a penetrating hydro-alcoholic vehicle containing a high concentration of active ingredient. Skin irritation was a problem. Subsequently, tretinoin cream and gel vehicles in a variety of concentrations became available. These formulations improved the irritation profile, but irritation was still a problem for some patients.
Two new topical delivery systems have been developed to deliver the active tretinoin while minimizing irritation. One delivery technique encapsulates tretinoin molecules in a microsphere that releases the active ingredient to the skin in a controlled manner. The microsphere is actually a porous synthetic polymer bead 10-25 microns in diameter. This delivery system has been used effectively to reduce the irritation of both tretinoin and benzoyl peroxide formulations. A second delivery technique for topical tretinoin is the polyolprepolymer-2 vehicle, which prevents rapid percutaneous absorption of the active ingredient and thus helps to alleviate irritation.

Another route to reducing the irritation potential of topical retinoids has been the development of third-generation retinoids that bind selectively to retinoid acid receptors (RARs). Adapalene, a modification of the tretinoin molecule that preferentially binds to RAR beta and RAR gamma, is highly effective, shows low irritation potential, and does not cause sensitization or photo-toxicity. Tazarotene is another third-generation retinoid that selectively binds to RARs, and topical formulations have been approved in the treatment of both acne and psoriasis.

Adapalene gel 0.1% and tretinoin microsphere gel 0.1% have been shown to have equivalent efficacy in a 12-week double-blind clinical trial, although tretinoin gel treatment achieved a significantly greater reduction in the number of comedones at week 4, suggesting that treatment with tretinoin microsphere might have a faster onset of action. Tretinoin-treated patients had more peeling and dryness compared with patients receiving adapalene, but erythema and burning/stinging was similar in the two patient groups.

In a 12-week double-blind clinical trial comparing once-daily application of tazarotene 0.1% gel with once-daily application of 0.1% tretinoin microsphere gel, both treatments achieved significant reductions in non-inflammatory and inflammatory lesion counts, although tazarotene achieved significantly greater reductions in non-inflammatory lesion counts at the end of treatment. Tazarotene also achieved greater reductions in overall disease severity by week 12 (36% reduction vs. 26% reduction, P = .2) both drugs were well tolerated.

Recent studies have investigated the cumulative irritancy potential of different topical retinoid molecules in various formulations. In a study comparing adapalene 0.1% cream and gel, tretinoin 0.025% in polyolprepolymer cream vehicle, tretinoin 0.025% and 0.05% creams, and tretinoin 0.1% microsphere gel (with white petrolatum used as a control), test materials were applied daily (Monday through Friday) for 21 days under occlusion to sites on the upper back for 24 hours. (Friday patches were left in place over the weekend.) Adapalene cream and gel formulations were significantly less irritating than the tretinoin formulations and not significantly more irritating than petrolatum. In a study of similar design that investigated adapalene 0.1% gel and solution, tazarotene 0.05% gel (this formulation is not indicated for acne) and 0.1% gel, tretinoin 0.1% microsphere gel, and tretinoin 0.025% polyolprepolymer cream and gel vehicle, adapalene gel and solution were significantly less irritating than both tazarotene gels, the tretinoin microsphere gel, and the tretinoin polyolprepolymer cream, and not significantly different from tretinoin in polyolprepolymer gel vehicle. Thirty-four of the 38 subjects who completed the study had to discontinue using the tazarotene formulations because of irritation; 7 discontinued the tretinoin microsphere gel; 3 discontinued tretinoin cream 0.025%; 1 discontinued tretinoin gel 0.025%; and 1 discontinued adapalene gel. No subjects discontinued adapalene solution or petrolatum.
The local reactions that may be associated with topical retinoids, including erythema, dry skin, pruritus, irritation, and burning/stinging can be moderated by the use of proper application techniques. This is especially important in adult patients who are more likely to have sensitive skin than are younger acne patients. Patients should wash their faces gently with tepid water and a mild cleanser and wait 20 minutes until their skin is completely dry before applying a pea-sized dose of the retinoid. Patients should also be instructed to apply sunscreen daily, use non-comedogenic moisturizers to reduce irritation, avoid sun exposure, and protect the face from cold, windy weather.