Keratolytic Treatments for Acne: A Review

By: Ali Alikhan, MD, Mayo Clinic; and Howard I Maibach, MD, University of California School of Medicine

Posted: September 29, 2010, from the October 2010 issue of Cosmetics & Toiletries.

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Topical retinoids encompass a group of powerful, comedolytic, anti-comedogenic and anti-inflammatory agents. They are powerful keratolytics, targeting both primary and secondary prevention of comedones. Mechanisms of action include: normalization of epidermal proliferation and differentiation, inhibition of neutrophil chemotaxis, expression of the toll-like receptors (TLRs) involved in immunomodulation, and anti-inflammatory effects via inhibition of prostaglandins, leukotrienes and interferon-gamma release.

With these treatments, local skin irritation and acne exacerbation, also termed retinoid flare, in some cases have occurred during the first month of retinoid treatment. A large, retrospective, vehicle-controlled study of mild/moderate to severe inflammatory acne demonstrated significant improvements with 0.1% tazarotene gel, 0.1% tazarotene cream, 0.1% adapalene gel and 0.1% tretinoin microsponge treatment. These treatments along with 0.025% tretinoin gel produced a significant improvement in global acne response. Among these, 0.1% tazarotene cream and 0.1% tazarotene gel showed greater improvement than adapalene gel and tretinoin gel. One study showed tazarotene to have the greatest efficacy on overall inflammatory acne severity and global response scales.³

Tretinoin: Tretinoin is an effective comedolytic and anti-comedogenic agent that increases epithelial cell turnover and modulates abnormal keratinization. Topical tretinoin has poor percutaneous absorption, and systemic retinoid levels remain constant despite application. Side effects of treatment with tretinoin include peeling, erythema, dryness, burning and itching. Adverse effects can be reduced by spacing out applications and/or diminishing the frequency and/or concentration of the product. Additionally, tretinoin should not be mixed with BPO (an oxidizing agent), which can result in degradation and deactivation of the tretinoin.

In a large multicenter trial, tretinoin significantly reduced inflammatory and non-inflammatory acne lesions by week 12, compared with a vehicle. Side effects of treatment with tretinoin included eruption, dry skin and exfoliation. Polyolprepolymer-2 (PP-2), which localizes drug molecules in upper skin layers, may diminish adverse cutaneous reactions. A large study demonstrated favorable global assessments with 0.025% tretinoin-PP-2 cream vs. 0.025% tretinoin cream, with no difference in tolerability.⁴

Recently, a hydrogel containing 1% clindamycin and 0.025% tretinoin was found more efficacious in treating inflammatory and non-inflammatory acne lesions than either agent alone or in a vehicle. These results were confirmed by two large studies; adverse events were similar in frequency and severity to tretinoin alone.⁵ Furthermore, a 6% BPO cleanser followed by 0.1% tretinoin microsphere gel demonstrated a greater inflammatory lesion reduction than tretinoin monotherapy.⁶