Modern possibilities of using systemic retinoids in dermatological practice (review of international literature) (in Russian only)

Matushevskaia E.V.; Svirshchevskaia E.V.

doi:https://doi.org/10.17116/klinderma20181705118

Close metadata

Recommended articles:

Clinical features of severe acne and genetic determinants of therapeutic efficacy of systemic isotretinoin. Russian Journal of Clinical Dermatology and Venereology. 2025;(1):30-37

Clinical and anamnestic features of rosacea in women in perimenopausal period. Russian Journal of Clinical Dermatology and Venereology. 2025;(1):49-55

Damage of human skin barrier components in exposure of Demodex specimens. Russian Journal of Clinical Dermatology and Venereology. 2025;(2):219-226

Experience of comprehensive treatment of erythematotelangiectatic rosacea. Russian Journal of Clinical Dermatology and Venereology. 2025;(2):236-239

Angiopausin concentrate for skin prone to redness. Russian Journal of Clinical Dermatology and Venereology. 2025;(3):369-374

On the issue of choosing anesthesia methods: a comparison of general medicine and clinical dentistry. Stomatology. 2025;(1):76-80

Comparing the efficacy of divozilimab and second-line treatments for relapsing-remitting multiple sclerosis in the Russian Federation: a systematic review and network meta-analysis. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(2):58-68

Efficacy and safety of fonturacetam in asthenia: a systematic review and meta-analysis. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(2):69-79

Experience of using ribociclib in the therapy of metastatic breast cancer in a regional oncological dispensary. P.A. Herzen Journal of Oncology. 2025;(3):89-93

Results of the international multicenter randomized, double-blind, placebo-controlled clinical trial for the evaluation of the efficacy and safety of the sequential therapy with ethylmethylhydroxypyridine succinate in patients in the acute and early recovery periods of ischemic stroke (MIR). S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(8-2):40-53

Abstract:

ABSTRACT This review presents the results obtained by the international clinical studies on the efficacy and safety of the systemic isotretinoin (SI) in the treatment of some dermatological disorders. The mechanisms of retinol and its derivative activity and the effects of synthetic analogs of retinol in diseases associated with keratinization processes are discussed. Multicenter randomized studies showed the effectiveness of SI in the treatment of focal alopecia, genital papillomas, plane warts, Kyrle’s disease, and some other dermatoses. International recommendations for SI management of different forms and severity acne and rosacea are presented. A wide spectrum of activity (comedonolytic, antiinflammatory, sebostatic, antiproliferative, antioxidant) suggests that SI can be used as the first-line treatment for severe and resistant forms of acne and rosacea. Recent clinical studies focus on the effects of SI on various safety parameters. The review provides the information on the new generation of SI with increased bioavailability, which enables course dose and side effects reduction. The advantages of isotretinoin formulation LIDOSE (compliance, efficacy, safety) for the treatment of acne and rosacea are discussed.

Keywords:

systemic isotretinoin

mechanisms of action

acne

rosacea

efficacy

safety

Authors:

Matushevskaia E.V.

FGOU Institut povysheniia kvalifikatsii Federal'nogo mediko-biologicheskogo agentstva RF, Moskva

Svirshchevskaia E.V.

Institut bioorganicheskoĭ khimii im. M.M. Shemiakina i Iu.A. Ovchinnikova RAN, Moskva, 117997, Rossiĭskaia Federatsiia

Close metadata

References:

Uray IP, Dmitrovsky E, Brown PH. Retinoids and rexinoids in cancer revention: from laboratory to clinic. Semin Oncol. 2016;43(1):49-64. https://doi.org/10.1053/j.seminoncol.2015.09.002
Sun H, Kawaguchi R. The membrane receptor for plasma retinol-binding protein, a new type of cell-surface receptor. Int Rev Cell Mol Biol. 2011;288:1-41. https://doi.org/10.1016/B978-0-12-386041-5.00001-7
Goodman AB. Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. J Cell Physiol. 2006;209(3):598-603.
Napoli JL. Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases. Pharmacol Ther. 2017;173:19-33. https://doi.org/10.1016/j.pharmthera.2017.01.004
Napoli JL. Functions of Intracellular Retinoid Binding-Proteins. Subcell Biochem. 2016;81:21-76.
Blaner WS. Retinoid Actions: A New Horizon. Endocrinology. 2017;158(9):2719-2721. https://doi.org/10.1210/en.2017-00622
Flajollet S, Staels B, Lefebvre P. Retinoids and nuclear retinoid receptors in white and brown adipose tissues: physiopathologic aspects. Horm Mol Biol Clin Investig. 2013;14(3):75-86. https://doi.org/10.1515/hmbci-2013-0013
Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992;68(2):397-406.
Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature. 1992;358(6389):771-774.
de Urquiza AM, Liu S, Sjöberg M, Zetterström RH, Griffiths W, Sjövall J, Perlmann T. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science. 2000;290(5499):2140-2144.
Lengqvist J, Mata De Urquiza A, Bergman AC, Willson TM, Sjövall J, Perlmann T, Griffiths WJ. Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics. 2004;3(7):692-703.
Amoutzias GD, Pichler EE, Mian N, et al. A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network. BMC Systems Biology. 2007;1:34. https://doi.org/10.1186/1752-0509-1-34
di Masi A, Leboffe L, De Marinis E, Pagano F, Cicconi L, Rochette-Egly C, Lo-Coco F, Ascenzi P, Nervi C. Retinoic acid receptors: from molecular mechanisms to cancer therapy. Mol Aspects Med. 2015;41:1-115. https://doi.org/10.1016/j.mam.2014.12.003
Al Tanoury Z, Piskunovm A, Rochette-Egly C. Vitamin A and retinoid signaling: genomic and nongenomic effects: thematic review series: fat-soluble vitamins: vitamin A. J. Lipid Res. 2013;54:1761-1775.
Schenk T, Stengel S, Zelent A. Unlocking the potential of retinoic acid in anticancer therapy. Br. J. Cancer. 2014;111:2039-2045. https://doi.org/10.1038/bjc.2014.412
Terao M, Nishida K, Murota H, Katayama I. Clinical effect of tocoretinate on lichen and macular amyloidosis. J Dermatol. 2011;38(2):179-184.
Patatanian E, Thompson DF. Retinoic acid syndrome: a review. J Clin Pharm Ther. 2008;33(4):331-338.
Vahlquist A. Long-term safety of retinoid therapy. J Am Acad Dermatol. 1992;27(6 Pt 2):S29-S33.
Eisenhardt EU, Bickel MH. Kinetics of tissue distribution and elimination of retinoid drugs in the rat. II. Etretinate. Drug Metab Dispos. 1994;22(1):31-35.
Hirschel-Scholz S, Siegenthaler G, Saurat JH. Isotretinoin differs from other synthetic retinoids in its modulation of human cellular retinoic acid binding protein (CRABP). Br J Dermatol. 1989;120(5):639-644.
Burney W, Bosanac SS, Nguyen C, Isseroff RR, Sivamani RK. Short-term exposure of human sebocytes to 13-cis retinoic acid induces acnegenic changes. Br J Dermatol. 2018. https://doi.org/10.1111/bjd.16837
Rühl R, Plum C, Elmazar MM, Nau H. Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid indicates differential cytosolic/nuclear localization. Toxicol Sci Off J Soc Toxicol. 2001;63:82-89.
Karadag AS, Ertugrul DT, Takci Z, Bilgili SG, Namuslu M, Ata N, Sekeroglu R. The effect of isotretinoin on retinol-binding protein 4, leptin, adiponectin and insulin resistance in acne vulgaris patients. Dermatology. 2015;230(1):70-74. https://doi.org/10.1159/000367687
Ahmad HM. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin. Dermatol Ther. 2015;28(3):151-157. https://doi.org/10.1111/dth.12213
Tagliolatto S, Santos Neto Ode O, Alchorne MM, Enokihara MY. Sebaceous hyperplasia: systemic treatment with isotretinoin. An Bras Dermatol. 2015;90(2):211-215. https://doi.org/10.1590/abd1806-4841.20153192
Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol. 2008;9(6):369-381. https://doi.org/10.2165/0128071-200809060-00003
Raza K, Singh B, Singla N, Negi P, Singal P, Katare OP. Nano-lipoidal carriers of isotretinoin with anti-aging potential: formulation, characterization and biochemical evaluation. J Drug Target. 2013;21(5):435-442. https://doi.org/10.3109/1061186X.2012.761224
Sarkar T, Sarkar S, Patra A. Low-dose isotretinoin therapy and blood lipid abnormality: A case series with sixty patients. J Family Med Prim Care. 2018;7(1):171-174. https://doi.org/10.4103/jfmpc.jfmpc_104_16
Kamal M, Polat M. Effect of different doses of isotretinoin treatment on the levels of serum homocysteine, vitamin B 12 and folic acid in patients with acne vulgaris: A prospective controlled study. J Pak Med Assoc. 2015;65(9):950-953.
Faghihi G, Mokhtari F, Fard NM, Motamedi N, Hosseini SM. Comparing the Efficacy of Low Dose and Conventional Dose of Oral Isotretinoin in Treatment of Moderate and Severe Acne Vulgaris. J Res Pharm Pract. 2017;6(4):233-238. https://doi.org/10.4103/jrpp.JRPP_17_30
Cannizzaro MV, Dattola A, Garofalo V, Del Duca E, Bianchi L. Reducing the oral isotretinoin skin side effects: efficacy of 8% omega-ceramides, hydrophilic sugars, 5% niacinamide cream compound in acne patients. G Ital Dermatol Venereol. 2018;153(2):161-164. https://doi.org/10.23736/S0392-0488.17.05742-X
Bettoli V, Zauli S, Borghi A, Toni G, Ricci M, Bertoldi AM, Virgili A. Efficacy and safety of a 12-month treatment with a combination of hydroxypinacolone retinoate and retinol glycospheres as maintenance therapy in acne patients after oral isotretinoin. G Ital Dermatol Venereol. 2017;152(1):13-17. https://doi.org/10.23736/S0392-0488.16.05201-9
Mysore V, Mahadevappa OH, Barua S, Majid I, Viswanath V, Bhat RM, Talwar S, Thurakkal S, Aurangabadkar SJ, Chatterjee M, Ganjoo A. Standard Guidelines of Care: Performing Procedures in Patients on or Recently Administered with Isotretinoin. J Cutan Aesthet Surg. 2017;10(4):186-194. https://doi.org/10.4103/JCAS.JCAS_110_17
Sbidian E, Vicaut É, Chidiack H, Anselin E, Cribier B, Dréno B, Chosidow O. A Randomized-Controlled Trial of Oral Low-Dose Isotretinoin for Difficult-To-Treat Papulopustular Rosacea. J Invest Dermatol. 2016;136(6):1124-1129. https://doi.org/10.1016/j.jid.2016.01.025
Schaller M, Almeida LM, Bewley A, Cribier B, Dlova NC, Kautz G, Mannis M, Oon HH, Rajagopalan M, Steinhoff M, Thiboutot D, Troielli P, Webster G, Wu Y, van Zuuren E, Tan J Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017 Feb;176(2):465-471.
Flores-Terry MÁ, García-Arpa M, Franco-Muñóz M, González-Ruiz L. Facial Papules in Frontal Fibrosing Alopecia: Good Response to Isotretinoin. Actas Dermosifiliogr. 2018. pii: S0001-7310(17)30668-3. https://doi.org/10.1016/j.ad.2017.08.018
Jha AK, Sonthalia S, Ganguly S. Oral isotretinoin as an adjunctive treatment for recurrent genital warts. J Am Acad Dermatol. 2018;78(2):e35-e36. https://doi.org/10.1016/j.jaad.2017.08.057
Maurelli M, Gisondi P, Girolomoni G. Kyrle’s disease effectively treated with oral isotretinoin. J Dermatolog Treat. 2018 Jan 10;1-3. https://doi.org/10.1080/09546634.2017.1422080
Forbat E, Ali FR, Al-Niaimi F. Dermatological indications for the use of isotretinoin beyond acne. J Dermatolog Treat. 2018;1-8. https://doi.org/10.1080/09546634.2018.1445194
Amory JK, Ostrowski KA, Gannon JR, Berkseth K, Stevison F, Isoherranen N, Muller CH, Walsh T. Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study. Andrology. 2017;5(6):1115-1123. https://doi.org/10.1111/andr.12420
Nast A, Dréno B, Bettoli V, Degitz K, Erdmann R, Finlay AY, Ganceviciene R, Haedersdal M, Layton A, López-Estebaranz JL, Ochsendorf F, Oprica C, Rosumeck S, Rzany B, Sammain A, Simonart T, Veien NK, Zivković MV, Zouboulis CC, Gollnick H; European Dermatology Forum. European evidence-based (S3) guidelines for the treatment of acne. J Eur Acad Dermatol Venereol. 2012;26(Suppl 1):1-29. https://doi.org/10.1111/j.1468-3083.2011.04374.x
Uslu M, Şavk E, Karaman G, Şendur N. Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema and sebum measurements. Acta Derm Venereol. 2012;92(1):73-77. https://doi.org/10.2340/00015555-1204
Pohl L, Karsai S, Raulin C. Rhinophyma: Successful treatment with low-dose oral isotretinoin. Hautarzt. 2018. https://doi.org/10.1007/s00105-018-4162-1
Howard R, Smith G. The readability of iPledge program patient education materials. J Am Acad Dermatol. 2018. pii: S0190-9622(18)30834-X. https://doi.org/10.1016/j.jaad.2018.05.038
Watson KD, Miest RY, Tollefson MM. Isotretinoin for acne and rosacea. Semin Cutan Med Surg. 2016;35(2):79-86. https://doi.org/10.12788/j.sder.2016.023
Pierson JC, Ferris LK, Schwarz EB. We Pledge to Change iPLEDGE. JAMA Dermatol. 2015;151(7):701-702. https://doi.org/10.1001/jamadermatol.2015.0736
Eichenfield LF, Krakowski AC. A novel patient support program to address isotretinoin adherence: proof-of-concept analysis. J Drugs Dermatol. 2015;14(4):375-379.
Verbeeck RK, De Niet S, Lebrun S, Tremege M, Rennie TW, Coffiner M, Streel B, Cahay B. The Lidose hard capsule formulation of fenofibrate is suprabioavailable compared to the nanoparticle tablet formulation under high-fat fed conditions. J Pharm Pharm Sci. 2015;18(1):61-67.
Webster GF, Leyden JJ, Gross JA. Results of a Phase III, double-blind, randomized, parallel-group, non-inferiority study evaluating the safety and efficacy of isotretinoin-Lidose in patients with severe recalcitrant nodular acne. J Drugs Dermatol. 2014;13(6):665-670.