Retinol molecule

Introduction

Retinoids such as tretinoin, adapalene, tazarotene and isotretinoin. are structural and functional analogues of vitamin A and are a common treatment option used to ameliorate acne, photodamage and post inflammatory hyperpigmentation. Retinoids may also act as penetration enhancers when used with other lightening agents such as hydroquinone and mequinol.

Mechanism of Action

The mechanism of action likely involves the inhibition of tyrosinase induction, the dispersion of keratinocyte pigmented granules and interference with pigment transfer. Other biological effects that result in skin depigmentation are expression of anti-inflammatory properties and a reduction in corneocyte cohesion with an associated modulation of cell proliferation and acceleration of epidermal cell turnover.

Retinoid Types

Topical tretinoin (all-trans-retinoic acid) is a naturally occurring metabolite of retinol and first-generation retinoid. Tretinoin is a derivative of vitamin A that is thought to have an inhibitory effect on tyrosinase transcription. Tretinoin is reported to be effective in treating melasma, with some associated side effects including erythema, peeling at the site of application and PIH. Though tretinoin monotherapy for hyperpigmentation and melasma is effective, it is slow and typically requires at least 24 weeks to see clinical improvement
Third-generation retinoids, adapalene and tazarotene, are synthetic topical agents with better cutaneous tolerability. Both agents have been shown in clinical studies to safely and effectively treat post inflammatory hyperpigmentation, particularly acne-induced post inflammatory hyperpimentation in darker skinned individuals.
Isotretinoin (13-cis-retinoic acid) is a naturally occurring, first-generation retinoid that is available in both oral and topical formulations. Oral isotretinoin is very effective in the treatment of severe acne; however, there has also been a case reported in the literature of significant resolution of post inflammatory hyperpigmentation after oral isotretinoin therapy in an asian patient.

Formulations

Adapalene is formulated in creams or gels in 0.1 to 0.3% concentrations; whereas, formulations of tazarotene include 0.05 and 0.1% creams or gels.
Tretinoin is available at different strengths ranging from 0.01% to 0.1%. It can be formulated in creams, gels, and microsphere gels, which allows for the controlled release of tretinoin leading to less irritation.
The use of tretinoin in concentrations of 0.05% - 0.1% as monotherapy for hyperpigmentation is common.
Tretinoin is often used in conjunction with hydroquinone and other topical creams and depigmenting agents to improve efficacy, such as a formulation proposed by Kligman and Willis containing 5% HQ, 0.1% tretinoin and 0.1% dexamethasone. Tretinoin in this formulation acts as a stimulant of epidermal turnover and pigment reduction via epidermopoieses, an antioxidant to reduce the oxidation of HQ and a mild irritant to enhance the epidermal penetration of HQ.

Studies

In a study on a white population, 0.1% tretinoin used as monotherapy reduced the over all severity of melasma by 36% compared with its vehicle. In a similar study, a 40-week, randomized, double-blind, vehicle-controlled clinical trial was conducted with 54 black patients to determine the safety and efficacy of 0.1% tretinoin in the treatment of post inflammatory hyperpigmentation. Tretinoin was significantly more effective than vehicle in lightening lesions when assessed by clinical (P<0.001) and colorimetric (P=0.05) analysis. However, 50 percent of patients developed retinoid dermatitis, which is the concern with using retinoids in skin of color. Starting at lower concentrations and titrating up based on treatment response and choosing more tolerable formulations, such as creams over gels, may help to decrease the risk of exacerbating PIH.
A randomized trial of 0.1% adapalene versus 0.05% tretinoin for 14 weeks in Indian patients with melasma showed a 41% reduction in MASI score in the adapalene group versus 37% reduction in the tretinoin group.

Adverse Effects

The most common adverse effects include burning, stinging, erythema, dryness, desquamation and scaling. Although the adverse effects are reversible, retinoid dermatitis may itself lead to postinflammatory hyperpigmentation, especially in dark-skinned individuals.