INTRODUCTION
Acne vulgaris affects approximately 85% of youths and can persist into adulthood.1-4 It is an inflammatory disease of the pilosebaceous unit and brought about by follicular hyperkeratinization, increased sebum production, and Cutibacterium (formerly Propionibacterium) acnes. Follicular dyskeratosis leading to formation of the microcomedo is believed to be central to the development of acne. The activation of innate and cellular immune responses subsequently occurs with genetics, androgens, diet, and stress also playing a role. Clinically, acne presents with open and closed comedones, inflammatory papules, pustules as well as nodules. It typically affects areas with greater density of sebaceous glands such as face, neck, chest, upper back, and upper arms.5-9 Although there are many treatment modalities for acne, scarring is an unfortunately common clinical outcome.10 Acne scars, which range from hypertrophic and keloidal to atrophic, arise due to delayed or inadequate treatment and healing of acne lesions.11-14 Atrophic scars are arguably the most frequently seen and can have significant impact on patients’ quality of life.15 The severity of scars is correlated with the extent of acne and the delay between disease onset and treatment initiation. Thus, one of the primary goals in acne treatment is adequately addressing the active disease in an effort to minimize potential permanent scarring.Retinoids are widely used in the management of acne. This class of medication targets the follicular dyskeratosis central to acne pathogenesis and also possesses anti-inflammatory properties. It has also been studied in the context of hyperpigmentation and scarring associated with acne. Here, we review the mechanism of action of retinoids, their topical and systemic use in acne vulgaris, their role in the management of acne scars, and early data on a new fourth generation retinoid, trifarotene.Retinoid Mechanism of ActionRetinoids are structural and functional analogues of vitamin A that exert multiple biological effects. The key to their efficacy is their ability to mediate their effects through their intranuclear retinoid receptors. Thus, a retinoid is defined as any molecule that, by itself or through metabolic conversion, binds to and activates the retinoic acid receptors, leading to activation of retinoic acid-responsive genes resulting in specific skin responses.16,17 Currently, retinoids are classified as first, second, and third generation retinoids. First generation retinoids include all-trans-retinoic acid (tretinoin), 13-cis-retinoic acid (isotretinoin), and 9-cis-retinoic acid (alitretinoin). Through replacement of the β-ionone ring in all-trans-retinoic acid with an aromatic structure, newer retinoids (or second-generation retinoids), were introduced, which include etretinate and acitretin. With the discovery of retinoic acid receptors, receptor-specific, third-generation retinoids such as adapalene and tazarotene were developed. As discussed below, a fourth-generation retinoid, trifarotene, is also on the horizon18 (Figure 1). The second, third, and fourth-generation retinoids are also known as synthetic retinoids as they bear no structural similarities to all-trans-retinol or retinoic acid yet are still considered
