Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD
and can only be employed once scarring has occurred. A topical retinoid offers an easier to use and more economical approach in acne scar treatment while preventing and targeting the persistent dermal tissue loss not addressed by many of the non-pharmacological treatments.Future Directions The area of retinoid research remains robust with the development of a new retinoid, trifarotene, on the horizon. This medication is the first fourth generation topical retinoid with potent and selective RARγ agonist activity with minimal RARβ-mediated effects, thus lending it greater efficacy with potentially decreased side effect of skin irritation. Furthermore, trifarotene has also been shown to possess increased hepatic instability compared to first and third generation retinoids, thus theoretically giving it a more tolerable systemic safety profile. This is an important consideration with more extensive topical use. In early studies, this medication demonstrated significant comedolytic and anti-inflammatory activities. Trifarotene was also shown to regulate many of the traditional retinoid-induced pathways. Its role in that regard along with its depigmenting properties can potentially expand its use in acne-related post-inflammatory hyperpigmentation and scarring.20
Acne vulgaris affects 85% of individuals 12-24 years of age and persistence into adulthood is not uncommon. Its pathogenesis centers around follicular dyskeratosis, increased sebum production, and Cutibacterium (formerly Propionibacterium) acnes. Acne can have tremendous psychosocial impact on the patient and can lead to permanent post-acne changes such as atrophic scarring. Retinoid is the cornerstone of acne treatment given it addresses the key pathogenic pathways in acne, which enables it to both treat and prevent acne. Furthermore, given its ability to downregulate MMPs seen with acne inflammation and restore dermal collagen, retinoid can also improve and prevent acne scars. Trifarotene is a new fourth generation topical retinoid with significant comedolytic, anti-inflammatory, and depigmenting properties. Its introduction to the acne therapeutic ladder will expand options for patients and further treatment success.
Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474?85.
White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol. 1998;39:S34?7.
Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999;41:577?80.
Canavan TN, Chen E, Elewski BE. Optimizing non-antibiotic treatments for patients with acne: A review. Dermatol Ther (Heidelb). 2016;6:555?78.
Jeremy AH, Holland DB, Roberts SG, et al. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121:20.
Lucky AW, Biro FM, Huster GA, et al. Acne vulgaris in premenarchal girls. An early sign of puberty associated with rising levels of dehydroepiandrosterone. Arch Dermatol. 1994;130:308.
Adebamowo CA, Spiegelman D, Danby FW, et al. High school dietary dairy intake and teenage acne. J Am Acad Dermatol. 2005;52:207.
Bataille V, Snieder H, MacGregor AJ, et al. The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol. 2002;119:1317.
Yosipovitch G, Tang M, Dawn AG, et al. Study of psychological stress, sebum production and acne vulgaris in adolescents. Acta Derm Venereol. 2007;87:135.
5. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol. 1994;19:303?8.
Goodman GJ, Baron JA. Postacne scarring: a qualitative global scarring grading system. Dermatol Surg. 2006;32:1458?66.
Fabbrocini G, Annunziata MC, D'Arco V, et al. Acne scars: pathogenesis, classification and treatment. Dermatol Res Pract. 2010;2010:893080.
Koo JY, Smith LL. Psychologic aspects of acne. Pediatr Dermatol. 1991;8:185?8.
Petkovich M, Brand NJ, Krust A, et al: A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987;330(6147):444-50.
Giguere V, Ong ES, Segui P, et al: Identification of a receptor for the morphogen retinoic acid. Nature. 1987;330(6149):624-9.
Thoreau E, Arlabosse JM, Bouix-Peter C, et al. Structure-based design of Trifarotene (CD5789), a potent and selective RARγ agonist for the treatment of acne. Bioorg Med Chem Lett. 2018;28(10):1736-1741.
Siddharth M, Abhijit D, Vandana P, et al. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1(4):327–348.
Aubert J, Piwnica D, Bertino B, et al. Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene. Br J Dermatol. 2018;179(2):442-456.
Yu VC, Delsert C, Andersen B, et al: RXR beta: A co-regulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response element. Cell. 1991;67(6):1251-66.
Kang S, Duell EA, Fisher GJ, et al: Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol. 1995; 105(4):549-56.
Aström A, Pettersson U, Chambon P, et al: Retinoic acid induction of human cellular retinoic acid-binding protein-II gene transcription is mediated by retinoic acid receptor retinoid X receptor heterodimers bound to one far upstream retinoic acid-responsive element with 5-base pair spacing. J Biol Chem. 1994;269(35):22334-9
Fisher GJ, Reddy AP, Datta SC, et al: All-trans retinoic acid induces cellular retinol-binding protein in vivo. J Invest Dermatol. 1995;105(1):80-6
Tenaud I, Khammari A, Dreno B. In vitro modulation of TLR-2, CD1d and IL- 10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol. 2007;16(6):500.
Liu PT, Krutzik SR, Kim J, et al. Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function. J Immunol. 2005;174(5):2467.
Ward A, Brogden RN, Heel RC, et al. Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders. Drugs.1984; 28:6.
Cunliffe WJ, Holland DB, Clark SM, et al. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol. 2000;142(6):1084- 91.
Millikan LE. The rationale for using a topical retinoid for inflammatory acne. Am J Clin Dermatol. 2003;4(2):75-80.
Griffiths CE, Kang S, Ellis CN, et al: Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: A double-blind, vehicle controlled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol. 1995;131(9):1037-44.
Culp L, Moradi Tuchayi S, Alinia H, et al. Tolerability of topical retinoids: are there clinically meaningful differences among topical retinoids? J Cutan Med Surg. 2015;19(6):530-8.
Tan J, Bissonnette R, Gratton D, et al. The safety and efficacy of four different fixed combination regimens of adapalene 0.1%/benzoyl peroxide 2.5% gel for the treatment of acne vulgaris: results from a randomised controlled study. Eur J Dermatol. 2018;28(4):502-508.
Buchan P, Eckhoff C, Caron D, et al: Repeated topical administration of all-trans-retinoic acid and plasma levels of retinoic acids in humans. J Am Acad Dermatol. 1994; 30(3):428-34.
Jick SS, Terris BZ, Jick H: First trimester topical tretinoin and congenital disorders. Lancet. 1993; 341(8854):1181-2.
Layton AM, Knaggs H, Taylor J et al: Isotretinoin for acne vulgaris: 10 years later: A safe and successful treatment. Br J Dermatol. 1993;129(3):292-6.
Cunliffe WJ, van de Kerkhof PC, Caputo R, et al: Roaccutane treatment guidelines: Results of an international survey. Dermatology. 1997;194(4):351-7.
Lee JW, Yoo KH, Park KY, et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol. 2011;164(6):1369-75.
Lehucher-Ceyrac D, Weber-Buisset MJ: Isotretinoin and acne: A prospective analysis of 188 cases over 9 years. Dermatology. 1993;186(2):123-8.
Tan J, Knezevic S, Boyal S, et al. Evaluation of Evidence for Acne Remission With Oral Isotretinoin Cumulative Dosing of 120-150 mg/kg. J Cutan Med Surg. 2016;20(1):13-20.
Lammer EJ, Chen DT, Hoar RM, et al: Retinoic acid embryopathy. N Engl J Med. 1985;313(14):837-41.
Koo J, Nguyen Q, Gambla C: Advances in psoriasis therapy. Adv Dermatol. 1997;12:47-72.
Williams RE, Doherty VR, Perkins W, et al: Staphylococcus aureus and intranasal mupirocin in patients receiving isotretinoin for acne. Br J Dermatol. 1992;126(4):362-6.
Ellis CN, Krach KJ. Uses and complications of isotretinoin therapy. J Am Acad Dermatol. 2001;45:S150.
Bonnetblanc JM, Hugon J, Dumas M, et al: Intracranial hypertension with etretinate. Lancet. 1983;2(8356):974.
Jick SS, Kremers HM, Vasilakis-Scaramozza C: Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000; 136(10):1231-6.
Etminan M, Bird ST, Delaney JA, et al. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol. 2013;149:216.
Safran AB et al: Ocular side-effects of oral treatment with retinoids. In: Retinoids: 10 Years On, edited by JH Saurat. Basel, Switzerland: Karger; 1991:315.
Kilcoyne RF: Effects of retinoids in bone. J Am Acad Dermatol. 1988;19(1 Pt 2):212-6.
Lee YH, Scharnitz TP, Muscat J, et al. Laboratory monitoring during isotretinoin therapy for acne: a systematic review and meta-analysis. JAMA Dermatol. 2016;152(1):35-44.
Wiegand UW et al: Treatment of female patients with isotretinoin: What is the safe post-therapy contraceptive period? Paper presented at Clinical Dermatology 2000. Vancouver, Canada, May 28-31, 1996.
Trivedi NR, Gilliland KL, Zhao W, Liu W, Thiboutot DM. Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol. 2006;126:1071?9.
Kang S, Fisher GJ, Voorhees JJ. Photoaging and topical tretinoin: therapy, pathogenesis, and prevention. Arch Dermatol. 1997;133:1280?4.
Riahi RR, Bush AE, Cohen PR. Topical retinoids: therapeutic mechanisms in the treatment of photodamaged skin. Am J Clin Dermatol. 2016;17(3):265-76.
Loss MJ, Leung S, Chien A, et al. Adapalene 0.3% gel shows efficacy for the treatment of atrophic acne scars. Dermatol Ther (Heidelb). 2018;8(2):245-257.
Dreno B, Tan J, Rivier M, et al. Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk of atrophic scar formation in moderate inflammatory acne: a split-face randomized controlled trial. J Eur Acad Dermatol Venereol. 2017;31(4):737-742.
Dréno B, Bissonnette R, Gagné-Henley A, et al. Prevention and reduction of atrophic acne scars with adapalene 0.3%/benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison. Am J Clin Dermatol. 2018;19(2):275-286.
Jacob CI, Dover JS, Kaminer MS. Acne scarring: a classification system and review of treatment options. J Am Acad Dermatol. 2001;45:109?17.
Privacy & Cookies Policy
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.