INTRODUCTION
Used for more than 50 years, tretinoin remains foundational in acne treatment, with nearly 2 million prescriptions written in 2019.1,2 The American Academy of Dermatology (AAD) and Global Alliance to Improve Outcomes in Acne (GA) recommend use of a topical retinoid alone or with benzoyl peroxide (BPO) as first-line treatment of inflammatory and noninflammatory acne across all severities.3,4 Additionally, topical tretinoin is approved by the US Food and Drug Administration (FDA) as an adjunctive agent in the palliation of fine facial wrinkles.5
Tretinoin use has historically been limited by poor tolerability and molecular instability.1,6 However, the development of new technologies may allow tretinoin use in patient populations and clinical situations previously not feasible (Figure 1).7
Tretinoin use has historically been limited by poor tolerability and molecular instability.1,6 However, the development of new technologies may allow tretinoin use in patient populations and clinical situations previously not feasible (Figure 1).7
REVIEW
History
The role of vitamin A in cell differentiation was discovered in 1925 when it was recognized that vitamin A deficiency in rats led to abnormal keratinization of epithelial cells.8 The link between vitamin A and skin disease was further elucidated in the 1930s when patients with vitamin A deficiencies were reported to exhibit cutaneous manifestations, including papular eruptions, xerosis, scaly skin, and increased incidence of diaper rash and intertrigo in infants.9 A second phase of research in the late 1930s to early 1940s suggested that patients with common skin conditions such as eczema, psoriasis, Darier disease, pityriasis rubra pilaris, and ichthyosis had lower than normal vitamin A levels. Many patients showed improvement when supplemented with supratherapeutic doses of vitamin A.9
In 1943, research demonstrated that large doses of oral vitamin A demonstrated acne improvement.10 These findings could not be replicated, but further research recognized oral vitamin A as "antikeratinizing."10
When given in the large doses required to treat skin disease (long-term treatment with >30,000 mcg daily or short-term treatment with >150,000 mcg daily),11 oral vitamin A caused numerous adverse effects (AEs), including increased intracranial pressure, headache, blurred vision, desquamation and peeling skin, alopecia, bone pain, cheilitis, hyperirritability, sleep disturbances, anorexia, and hepatomegaly, among others.10,12 With the hope of demonstrating therapeutic benefit without producing the systemic toxicities seen with oral treatment, topical vitamin A (retinol) was then studied in the treatment of dyskeratotic conditions but failed to exhibit efficacy.10,13
The role of vitamin A in cell differentiation was discovered in 1925 when it was recognized that vitamin A deficiency in rats led to abnormal keratinization of epithelial cells.8 The link between vitamin A and skin disease was further elucidated in the 1930s when patients with vitamin A deficiencies were reported to exhibit cutaneous manifestations, including papular eruptions, xerosis, scaly skin, and increased incidence of diaper rash and intertrigo in infants.9 A second phase of research in the late 1930s to early 1940s suggested that patients with common skin conditions such as eczema, psoriasis, Darier disease, pityriasis rubra pilaris, and ichthyosis had lower than normal vitamin A levels. Many patients showed improvement when supplemented with supratherapeutic doses of vitamin A.9
In 1943, research demonstrated that large doses of oral vitamin A demonstrated acne improvement.10 These findings could not be replicated, but further research recognized oral vitamin A as "antikeratinizing."10
When given in the large doses required to treat skin disease (long-term treatment with >30,000 mcg daily or short-term treatment with >150,000 mcg daily),11 oral vitamin A caused numerous adverse effects (AEs), including increased intracranial pressure, headache, blurred vision, desquamation and peeling skin, alopecia, bone pain, cheilitis, hyperirritability, sleep disturbances, anorexia, and hepatomegaly, among others.10,12 With the hope of demonstrating therapeutic benefit without producing the systemic toxicities seen with oral treatment, topical vitamin A (retinol) was then studied in the treatment of dyskeratotic conditions but failed to exhibit efficacy.10,13
