The Evolution of Topical Retinoids in Dermatology: A Cornerstone of Acne Management (1971-2025)

Topical retinoids have been a cornerstone in the management of acne vulgaris for over 5 decades, and they remain important even as treatment paradigms evolve. There is an ongoing need to understand the history and context of current retinoid use to support future innovations and improvements in the care of patients with acne.

Peer-reviewed literature was searched to identify articles related to topical retinoids, including their development, receptor selectivity, mechanisms of action, efficacy, tolerability, and role in the treatment of acne and management of acne sequelae.

Molecular design for stability and receptor-specific activity distinguishes the retinoid generations. Increased selectivity for retinoic acid receptor γ (RARγ) has changed the profile of modulated genes, with many of the altered genes having known roles with implications in the pathogenesis of acne and acne sequelae. Finally, the potential of retinoids to manage acne sequelae, such as atrophic scarring and acne-induced hyperpigmentation, has been demonstrated in clinical trials.

Most available studies are heterogeneous in design, with few large-scale trials directly comparing newer selective RARγ agonists with older agents. Moreover, long-term safety data beyond 1 year are limited, and real-world adherence metrics are underreported. Finally, formulation variability across studies complicates direct efficacy and tolerability comparisons.

Advancements in the selectivity of retinoids, adjunctive skincare, and patient education have reduced adverse effects of topical retinoids and improved adherence. A thorough understanding of retinoid biology and pharmacology is essential for dermatologists to optimize patient outcomes and maximize the therapeutic potential of this important drug class.