Since their therapeutic use took root in the late 1960s, topical retinoids have become perhaps the most versatile creams on the market. Dr Jeremy O’Kennedy lifts the veil on the vast spectrum of dermatological conditions that benefit from their application.
The modern history of retinoids began in the early 20th century when vitamin A (retinol) was identified within the humble egg yolk as being vital to embryo development. Since these early days, evidence has mounted to indicate new avenues of therapeutic benefit and potential. This has established retinoids as arguably the most versatile topicals available to medical science, and their use spectrum is so wide that it is often possible to address multiple conditions simultaneously.
Why retinoids work
The key to the remarkable therapeutic benefits of topical retinoids lies in their ability to regulate abnormal cellular proliferation and decrease inflammation. Specifically, they can help normalise hyperkeratinization (a thickening of the outermost skin layer) due to abnormal growth and differentiation in keratinocytes and other epidermal cell lines.1
Their potent anti-inflammatory and even anti-tumour effects stem from their suppression of various immune factors, including the activity of leukocytes, the release of pro-inflammatory cytokines and other mediators, as well as the expression of transcription factors and toll receptors involved in immunomodulation (changes in the immune system).2
Topical retinoids have also proven to be effective against the modern scourge of antibiotic resistance, as they assist in controlling inflammatory and non-inflammatory acne lesions – thereby reducing the how often antibiotics are used.3 It is important to note that, because of significant structural differences, the newest generation of retinoids are quite dissimilar to over-the-counter retinols (all-trans retinol), both in their pharmacology and therapeutic effects.4
The literature indicates that the implied benefits of some OTC products may potentially occur because all-trans retinol oxidises, forming tretinoin, after its absorption into skin cells (Prystowsky, 2001). When it comes to OTC forms, it is difficult, however, to determine the actual amount of the active agent such unregulated products contain. Further, many of these products contain biologically inactive forms.
On the other side, topical retinoids that only available by prescription can provide favourable, evidence-based results. They should be what is recommended and prescribed in evidence-based dermatology practices, rather than pointing patients to OTC retinol cosmeceutical products.
How they work
The basis of retinoid activity stems from interactions with the retinoic nuclear receptors on cells. This also activates genes that contain retinoic acid response elements or retinoic X response elements in their promoters (Michel, Jombard & Démarchez, 1998). Retinoids have also been shown to regulate gene expression by inhibiting the activity of other transcription factors, such as AP-1. Studies further show that the AP-1 complex may play a substantial role in primary inflammatory and immune responses.5
A plethora of clinical uses
Topical retinoids should be prescribed widely in modern, evidence-based dermatology practice – for both numerous established indicated purposes and several worthwhile, evidence-based, off-label uses. Below is a relatively extensive list of conditions that should be treated with the use of topical retinoids.
Acne Vulgaris
After more than 30 years, retinoids remain the gold standard and cornerstone in the treatment of acne vulgaris. They demonstrate unrivalled anti-comedogenic properties, leading to a reduction in microcomedo (tiny clogged pore) formation, which is a precursor of both inflammatory and non-inflammatory acne lesions.6
Retinoic acid (tretinoin) reverses the thickening of the skin’s outermost layer and the abnormal peeling of skin cells (keratinocytes specifically), and has been a mainstay in the treatment of acne for more than 30 years.7
Clinicians should consider using a topical retinoid for first-line management for mild to moderate acne treatment. According to the literature, a 12-week double-blind study was conducted to evaluate the efficacy and safety of tretinoin microsphere 0.1% gel with adapalene 0.1% gel in the treatment of acne. Both drugs demonstrated similar efficacy in the resolution of acne, but tretinoin microsphere gel may result in a faster action in reducing comedones, compared to adapalene.8
Photodamage & Photo-ageing
The observable signs of photoageing – such as wrinkling, rough texture, dyspigmentation, hypotonia and dullness – are largely caused by the effects of long-term radiation damage due to UV exposure.
Numerous studies support the recommendation of topical tretinoin to help reverse and prevent photodamage.
A 1986 breakthrough publication by Dr Albert Klingman and colleagues helped to open the door for further supportive research. After noting that their well-controlled, middle-aged female acne patients were reluctant to discontinue tretinoin therapy – in view of a perceived improvement in fine lines and general skin appearance while using tretinoin – Klingman’s interest was piqued.9
Tretinoin protects the skin against damage from UVA and UVB rays, it enhances the ability of the papillary dermis to prevent collagen loss and degradation10,11. Patients treated with topical tretinoin develop an increased awareness of the adverse effects of sun exposure and an increased motivation to employ sunscreens and sun avoidance as additional means of preventing skin damage12. Tretinoin is often used before and after skin resurfacing and adjunctively with other cosmetic procedures to enhance and maintain results.
Psoriasis
The major pathologic anomalies in psoriasis are epidermal hyperproliferation (excessive skin cell production) and parakeratosis (nucleated keratinocytes appearing in the outermost skin layer). Tazarotene was developed as an antipsoriatic drug in view of its anti-proliferative, anti-inflammatory and plaque thinning effects13. Other topical retinoids have also shown effective therapeutic benefits in the control of psoriasis, especially on facial psoriatic lesions.
Actinic Keratoses, Neoplasms & Lentigines
Topical retinoids have demonstrated efficacy in the treatment of actinic keratoses (AKs) and actinic lentigines. This is not surprising, considering their ability to decrease melanogenesis, antiproliferative effect, antipromoter effect, and prodifferentiation effect14. Topical tretinoin decreases the number of AKs on the face by approximately 50% when used over a minimum of six months15.
Because of topical tretinoin’s ability to normalise the differentiation of dysplastic epithelium in AKs, it can be considered for chemoprevention in patients at high risk of basal or squamous cell carcinomas – especially in transplant recipients and those vulnerable due to systemic immunosuppressive agents. Topical retinoids can provide an often-favourable alternative to cryotherapy and other destructive regimens in persons with multiple lesions16.
The application of tretinoin has demonstrated an effective suppressive effect on oral leukoplakias, and treatment may be justified in those patients with recurrent and persistent lesions17.
Rosacea
Topical tretinoin cream has demonstrated benefit in multiple subtypes of rosacea, including severe recalcitrant disease18. Its application can minimise the manifestations of papular-pustular rosacea within a relatively short time19.
Verruca
Topical tretinoin has demonstrated favourable results for treating verruca plantaris and verruca plana20. Topical tretinoin is often beneficial when treating facial verruca, especially when disseminated planar warts are present. Treating facial verruca with tretinoin is less irritative and is comparatively efficacious to imiquimod.
Scars, Keloids & Striae
Topical retinoids lead to increased epidermal proliferation and new collagen formation, which contribute to an improvement in hypertrophic scars, keloids and acne scars. It has also demonstrated significant improvements in the appearance of pregnancy-related striae (stretch marks) in multiple clinical trials21. Other non-pregnancy-related striae have also demonstrated good and lasting treatment responses.
Lichen Planus
Topical tretinoin is an effective maintenance therapy for cutaneous lichen planus and can contribute to preventing its recurrence22. Topical tazarotene has demonstrated significant therapeutic benefits in the treatment of resistant oral lichen planus23.
Dyspigmentation & Melasma
Combination therapy that includes strict photoprotection, topical hydroquinone and topical tretinoin remains the gold standard in the treatment of melasma. Tretinoin is reasonably well tolerated and also increases the efficacy of hydroquinone24.
Darier’s disease
Both oral and topical retinoids are effective in treating Darier’s disease. Oral retinoids are the most effective treatment, but are associated with troublesome side effects. Case studies have reported favourable success regarding the use of tazarotene gel, adapalene gel and tretinoin gel for this disorder25.
Wound Healing
The use of topical retinoids in wound healing is flourishing and studies have demonstrated that tretinoin dramatically accelerates healing in photodamaged skin26. Its topical application reverses the inhibitory effects of glucocorticoids on wound healing and expedites the formation of healthy granulation tissue.
A comparison of tretinoin, adapalene and collagenase in an experimental model of wound healing concluded that tretinoin and adapalene contributed to the wound healing process, resulting in an enhancement of collagen production, angiogenesis and granulation tissue formation27.
Tretinoin is also effective in accelerating wound healing when applied before treatments that cause epidermal injury, such as chemical peeling and dermabrasion.
Granular Parakeratosis
In treating granular parakeratosis, topical tretinoin has been shown to lead to a rapid clearance of lesions in the armpits in case studies28.
Osteoma Cutis
The local application of tretinoin decreases the number of facial papules in osteoma cutis. Tretinoin cream should be considered in treating multiple miliary osteoma cutis of the face, especially when dealing with small and superficial lesions29.
Alopecia Areata
In evaluating the safety and efficacy of 0.05% tretinoin and adjunctive intra-lesional triamcinolone for treating alopecia areata, topical tretinoin appeared to enhance the hair-growth-producing effect of the intralesional triamcinolone. Tretinoin helps to normalise cell differentiation, and the familiar retinoid dermatitis may contribute to the stimulation of hair growth by creating an immune response. Coupling topical tretinoin with topical minoxidil has also showed promising results for treating alopecia areata.
Keratosis Pilaris
Topical tretinoin reduces adherence among keratinised cells, thus leading to a rapid improvement and the prevention of keratosis pilaris lesions. It is recommended to start with a low dose and frequency of tretinoin and gradually increase these, as tolerated.
Acanthosis Nigricans
A synergistic combination of topical tretinoin at bedtime and 12% ammonium lactate lotion twice daily has shown an 85% to 95% improvement of acanthosis nigricans presenting on the neck, which is associated with obesity30.
Take-home message
While there is no silver bullet or holy grail in the realm of medical science, topical retinoids may just be the closest such medication we have in the dematological space. Its versatility is unparalleled and it should be widely prescribed by practitioners in the field.
Disclaimer: This article was commissioned by Rite Aid Health Care, though the article therein is based on Dr Jeremy D. O’Kennedy’s professional experience and opinion. Rite Aid is the distributor of medical-grade retinol in South Africa available by prescription only. Due to medical regulations in South Africa, we are unable to publish the names of scheduled medicines. Contact Rite Aid for more info (+27) 011 325 2686 / info@riteaid.co.za or contact your doctor for more information.
Written by Dr Jeremy D. O’ Kennedy

Dr Jeremy D. O’ Kennedy
Specialist Dermatologist
MBChB, FCDerm (SA), MMed
- Awarded with a Nelson Mandela medal for his work during the Lagos church collapse and funeral of the late president
- Certification in Aviation Medicine (PRET)
- Certification in Travel Medicine (Wits)
- Certification in Disaster Medicine (SEMPER/Stanford)
- Served as special advisor to the HoD/Premier on the FSP COVID-19 War Room
- www.facebook.com/Dr-Jeremy-D-OKennedy-MBChB-FCDerm-MMed-Specialist-Dermatologist
References:
- American Academy of Dermatology. (2003). Actinic keratoses net. Retrieved from www.skincarephysicians.com/actinickeratosesnet/treatment.htm
- Wolf, J.E. (2002). Potential anti-inflammatory effects of topical retinoids and retinoid analogues. Advances in Therapy, 19(3), 109-118.
- Rizova, E., Pagnoni, A., Stoudemayer, T., Poncet, M., & Kligman, A.M. (2001). Polarized light photography and videomicroscopy greatly enhance the capability of estimating the therapeutic response to a topical retinoid (adapalene) in acne vulgaris. Cutis, 68(4S), 25-33.
- Baumann, L.S. (2003, July). Topical treatments for photodamage. Skin & Allergy News – New Directions in the Uses of Retinoid Therapy in Cosmetic Dermatology (Suppl.).
- Michel, S., Jombard, A., & Démarchez, M. (1998). Pharmacology of adapalene. British Association of Dermatology, 139(52), 3-7.
- Leyden, J., Lowe, N., Kakita, L., & Draelos, Z. (2001). Comparison of treatment of acne vulgaris with alternate-day applications of tazorotene 0.1% gel and once-daily applications of adapalene 0.1% gel: A randomized trial. Cutis, 67(6 Suppl.), 10-16.
7. 20,22. Verschoore, M., Bouclier M., Czernielewski, J., & Hensby, C. (1993). Topical retinoids – their uses in dermatology. Dermatologic Clinics, 11(1), 107-113.
- Nyirady, J., Grossman, R.M., Nighland, M., Berger, R.S., Jorizzo, J.L. et al. (2001). A comparative trial of two retinoids commonly used in the treatment of acne vulgaris. Journal of Dermatologic Treatment, 12(3), 149-157.
- Klingman, A.M., Grove, G.L., Hirose, R., & Leyden, J.J. (1986). Topical tretinoin for photoaged skin. Journal of the American Academy Dermatology, 15, 836-859.
- Francz, P.I., Conrad, J., & Biesalski, H.K. (1998). Modulation of UVA-induced lipid peroxidation and suppression of UVB-induced ornithine decarboxylase response by all-trans-retinoic-acid in human skin fibroblasts in vitro. Biological Chemistry, 379, 1263-1269.
- Griffiths, C.E. (2001). The role of retinoids in the prevention and repair of aged and photoaged skin. Clinical and Experimental Dermatology, 26(7), 613-618.
- Weinstein, G.D., Nigra, T.P., Pochi, P.E., Savin, R.C., Allan, A. et al. (1991). Topical tretinoin for treatment of photodamaged skin. Archives of Dermatology, 127, 659-665.
13. 15. Prystowsky, J.H. (2001). Topical retinoids. In S.E. Wolverton, Comprehensive dermatologic drug therapy (pp. 578-594). Philadelphia: W.B. Saunders Company.
- Stockfleth, E., Ulrich, C., Meyer, T., & Christophers, E. (2002). Epithelial malignancies in organ transplant patients: Clinical presentation and new methods of treatment. Recent Results Cancer Research, 160, 251-258.
- Gorsky, M., & Epstein, J.B. (2002). The effect of retinoids on pre-malignant oral lesions: Focus on topical therapy. Cancer, 95(6), 1258-1264.
- Ertl, G.A, Levine N., & Klingman, A.M. (1994). A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Archives of Dermatolology, 130(3), 19-24.
- Bergfeld, W.F. (1999). A lifetime of healthy skin: Implications for women. International Journal of Fertility, 44(2), 83-95.
- Rangel, O., Arias, I., Garcia, E., & Lopez-Padilla, S. (2001). Topical tretinoin 0.1% for pregnancy-related abdominal striae: An open-label, multicenter, prospective study. Advances in Therapy, 18(4), 181-186.
- Petruzzi, M., De Benedittis, M., Grassi, R., Cassano, N., Vena, G. et al. (2002). Oral lichen planus: A preliminary clinical study on treatment with tazarotene. Oral Diseases, 8(6), 291-5.
- Pathak, M.A., Fitzpatrick, T.B., & Kraus, E.W. (1986). Usefulness of retinoic acid in the treatment of melasma. Journal of the American Academy of Dermatology, 15(4), 894-899.
- English, J.C. (2000, November). Topical treatment options for Darier’s disease. Skin & Aging: Targeting New Uses for Retinoids (Suppl.).
- Popp, C., Klingman, A.M., & Stoudemayer, T.J. (1995). Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds. British Journal of Dermatology, 132(1), 46-53.
- Basak, P.Y., Eroglu, E., Altuntas, I., Agular, F., Basak, K. et al. (2002). Comparison of the effects of tretinoin, adapalene, and collagenase in an experimental model of wound healing. European Journal of Dermatology, 12(2), 145-8.
- Brown, S.K., & Heilman, E.R. (2002). Granular parakeratosis: Resolution with topical tretinoin. Journal of the American Academy of Dermatology, 47(5 Suppl.), S279-280.
- Cohen, A.D, Chetov, T., Cagnano, E., Naimer, S., & Vardy, D.A. (2001). Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all-trans-retinoic acid): A case report and review of the literature. Journal of Dermatologic Treatment, 12(3), 171-173.
- Blobstein, S.H. (2003). Topical therapy with tretinoin and ammonium lactate for acanthosis nigricans associated with obesity. Cutis, 71(1), 33.
Rochelle is the founder and driving force behind Aesthetic Appointment. With a passion for the aesthetics and pro-ageing industry in South Africa, she has been in the aesthetic publishing industry since 2012, dedicated to creating a valuable platform for insights and knowledge, bridging the gap between patients and doctors - delivering reliable, medical-based information. Rochelle firmly believes in the power of a good skincare regimen, especially when started at home, and is committed to educating consumers about the myriad of treatments, procedures, and products available to them.