ISOTRETINOIN FOR TREATING ACNE VULGARIS

  • IRMA BERNADETTE S. SITOHANG Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia

Abstract

Acne vulgaris (AV) occurs in more than 80% of dermatological cases in adolescents and young adults and affects the quality of life. Oral isotretinoin, a metabolite product of vitamin A, is well-known to be the most effective treatment for severe nodulocystic AV and moderate AV that does not respond to other therapeutic modalities. Thus, this literature review was conducted to explain the mechanism of action, effectiveness, contraindications, side effects, and safety of oral isotretinoin in AV, which provided essential information for dermatologists. Furthermore, isotretinoin is the only treatment modality that has implications for the entire pathogenesis of acne. It contributes to decreasing corneocytes’ adhesion, supporting cellular proliferation and follicular renewal, induction of cell apoptosis, and immune regulation. The effectiveness of AV therapy with isotretinoin has expanded as it is also indicated for moderate to severe AV that does not respond well to topical combination therapy or systemic antibiotics. However, isotretinoin is included in Category X drugs and may induce many side effects from mucocutaneous effects to teratogenicity. From this extensive literature review, it can be concluded that isotretinoin is one of the treatment modalities for acne with good effectivity due to its mechanism of actions that affect the entire acne pathogenesis. Considering the various side effects of isotretinoin, its use requires adequate clinical assessment and monitoring by a dermatologist.

Keywords: Acne vulgaris, Isotretinoin, Effectiveness, Contraindications, Side effects, Safety

References

1. Wahab MA, Rahman MH, Monamie NS, Jamaluddin M, Khondker L, Afroz W. Isotretinoin versus weekly pulse dose azithromycin in the treatment of acne–a comparative study. J Pakistan Assoc Dermatol 2008;18:9-14.
2. Ayanoglu BT, Demirdag HG, Armagan BY, Bezirgan O. Perceptions about oral isotretinoin treatment. Dermatol Ther 2009;32:e12873.
3. Brzenzinski P, Borowska K, Chiriac A, Smigielski J. Adverse effects of isotretinoin: a large, retrospective review. Dermatol Ther 2017;30:e12483.
4. Bettoli V, Guerra Tapia A, Herane MI, Piquero Martin J. Challenges and solutions in oral isotretinoin in acne: reflections on 35 y of experience. Clin Cosmet Investig Dermatol 2019;12:943-51.
5. Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN. Acne therapy: a methodologic review. J Am Acad Dermatol 2002;47:231-40.
6. Zanglein AL, Pahy A, Scholsser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-73.
7. Rademaker M, Wishart JM, Birchall NM. Isotretinoin 5 mg daily for a low-grade adult can vulgaris–a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol 2014;28:747-54.
8. Layton A. The use of isotretinoin in acne. Dermatoendocrinol 2009;1:162-9.
9. Bagatin E, Costa CS. The use of isotretinoin for acne–an update on optimal dosing, surveillance, and adverse effects. Expert Rev Clin Pharmacol 2020;13:885-97.
10. Wiegand UW, Chou RC. Pharmacokinetics of oral isotretinoin. J Am Acad Dermatol 1998;39 Suppl 2:S8-12.
11. Wyss R, Bucheli F. Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching: I. Determination of isotretinoin and tretinoin and their 4-oxo metabolites in plasma. J Chromatogr 1988;424:303-14.
12. Lefebvre P, Thomas G, Gourrnel B. Pharmacokinetics of oral all-trans-retinoic acid in patients with acute promyelocytic leukemia. Leukemia 1991;5:1054-8.
13. Fogh K, Voorhees JJ, Astrom A. Expression, purification and binding properties of human cellular retinoic acid-binding protein type I and II. Arch Biochem Biophys 1993;300:751-5.
14. Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, et al. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 1993;90:30-4.
15. Levin AA, Bosakowski T, Kazmer S, Grippo JF. 13-cis retinoic acid does not bind to retinoic acid receptors alpha, beta and gamma. Toxicologist 1992;12:181.
16. Ott F, Bollag W, Geiger JM. Oral 9-cis-retinoic acid versus 13-cis-retinoic acid in acne therapy. Dermatology 1996;193:124-6.
17. Geiger JM, Hommel L, Harms M, Saurat JH. Oral 13-cis-retinoic acid is superior to 9-cis-retinoic acid in sebosuppression in human beings. J Am Acad Dermatol 1996;34:513-5.
18. Tsukada M, Schröder M, Roos TC, Chandraratna RA, Reichert U, Merk HF, et al. 13-cis-retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans-retinoic acid and binding to retinoid acid receptors. J Invest Dermatol 2000;115:321-7.
19. Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis-retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol 2006;126:2178-89.
20. Al-Abadie M, Oumeish F, Al-Rubaye M, Rafiq S, Ball PA, Morrissey H. Vitamin A derivatives use in the treatment of skin conditions. Int J Curr Pharm Sci 2020;12:9–12.
21. Knutson DD. Ultrastructural observations in acne vulgaris: the normal sebaceous follicle and lesions. J Invest Dermatol 1974;62:288-307.
22. Plewig G, Dressel H, Pfleger M, Michelsen S, Kligman AM. Low-dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne. J Dtsch Dermatol Ges 2004;2:31-45.
23. Dalziel K, Barton S, Marks R. The effects of isotretinoin on follicular and sebaceous gland differentiation. Br J Dermatol 1987;117:317-23.
24. Shetti SA, Nagesh HN, Hanumantharaya N. A randomized, open-label, comparative study of the efficacy of low-dose continuous versus low-dose intermittent oral isotretinoin therapy in moderate-to-severe acne vulgaris. Natl J Physiol Pharm Pharmacol 2017;7:941-6.
25. El-Sherif NA, Greiw AS, Benamer AM. Efficacy of low dose versus intermittent isotretinoin regimens in patients with moderate acne vulgaris: a randomized controlled trial. Ibnosina J Med Biomed Sci 2013;5:296-302.
26. Kaymak Y, Ilter N. The effectiveness of intermittent isotretinoin treatment in mild or moderate acne. J Eur Acad Dermatol Venereol 2006;20:1256-60.
27. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol 2006;54:644-6.
28. Costa CS, Bagatin E, Matimbianco ALC, da Silva EMK, Lucio MM, Magin P, et al. Oral isotretinoin for acne. Cochrane Database Syst Rev 2018:CD009435. DOI:10.1002/14651858. CD009435.pub2
29. Akman A, Durusoy C, Senturk M, Koc CK, Soyturk D, Alpsoy E. Treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled, multicenter study. Arch Dermatol Res 2007;299:467-73.
30. Piquero Martin J, Misticone S, Piquero Casals V, Piquero Casals J. Topic therapy-mini isotretinoin doses vs topic therapy-systemic antibiotics in the moderate acne patients. Ann Dermatol Venereol 2002;129:S382.
31. Strauss JS, Rapini RP, Shalita AR, Konecky E, Pochi PE, Comite H, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 1994;10:490-6.
32. Shalita AR. Acne revisited. Arch Dermatol 1994;130:363-4.
33. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris-10 y later: a safe and successful treatment. Br J Dermatol 1993;129:292–6.
34. Azoulay L, Oraichi D, Berard A. Isotretinoin therapy and the incidence of acne relapse: a nested case-control study. Br J Dermatol 2007;157:1240-8.
35. Prevost N, English J. Isotretinoin: update on controversial issues. J Pediatr Adolesc Gynecol 2013;26:290-3.
36. Charrow A, Xia FD, Lu J, Waul M, Joyce C, Mostaghimi A. Differences in isotretinoin start, interruption, and early termination across race and sex in the iPLEDGE era. PLoS One 2019;14:e0210445.
37. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-73.
38. Eichenfield LF, Krakowski AC. A novel patient support program to address isotretinoin adherence: proof-of-concept analysis. J Drugs Dermatol 2015;14:375-9.
39. Tripathi SV, Gustafson CJ, Huang KE, Feldman SR. Side effects of common acne treatments. Expert Opin Drug Saf 2013;12:39-51.
40. McLane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol 2001;45:S188-94.
41. Zomerdijk IM, Ruiter R, Houweling LMA, Herings RMC, Sturkenboom MCJM, Straus SMJM, et al. Isotretinoin exposure during pregnancy: a population-based study in the netherlands. Br Med J Open 2014;4:e005602.
42. Premchandran D, Madhyastha S, Sahu S, Joy T, Rachana K. Effect of prenatal isotretinoin on postnatal development of rat retina and expression of doublecortin positive cells: a morphometric and histopathological analysis. Int J Pharm Pharm Sci 2014;6:622-6.
43. Rademaker M. Adverse effects of isotretinoin: a retrospective review of 1743 patients started on isotretinoin. Australas J Dermatol 2010;51:248-53.
44. Opel D, Kramer ON, Chebvalier M, Bigby M, Albrecht J. Not every patient needs a triglyceride check, but all can get pancreatitis: a systematic review and clinical characterization of isotretinoin-associated pancreatitis. Br J Dermatol 2017;177:960-6.
45. Tanngoen P, Lamlertthon S, Tiyaboonchai W. Effects of alpha-mangostin and citronella oil against acne-causing bacteria. Int J Pharm Pharm Sci 2019;11:45–9.
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SITOHANG, I. B. S. (2021). ISOTRETINOIN FOR TREATING ACNE VULGARIS. International Journal of Applied Pharmaceutics, 13(2), 20-25. https://doi.org/10.22159/ijap.2021v13i2.40045
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Review Article(s)