The Role of Different Factors in Pathophysiology of Acne and Potential Therapeutic Options: A Brief Review

Document Type : Review Article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

3 School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

4 School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Acne vulgaris is a chronic multifactorial skin disease that millions of people around the world of suffering from that. Pathophysiology of acne consists of several mechanisms including hyper-seborrhea, hyperkeratinization of pilosebaceous units, increased bacterial proliferation, hyperandrogenism, alteration in sebum contents, and inflammatory processes. In this regard, consideration of the main causes of acne development and severity of acne lesions in the selection of suitable pharmacologic agents is essential. In this review, among the other factors, the role of the different lipids in pathophysiology of acne were considered. The common sources of skin lipids have been categorized into two main categories including endogenous and exogenous sources. Furthermore, the role of different factors including lipids and fatty acids, androgens, microorganisms, cosmeceuticals, and lipids oxidation and peroxides in acne vulgaris development have been summarized. In the end, the necessity of the choice of appropriate pharmacotherapy regimens and recruitment of novel drug delivery systems in acne management have been mentioned. 
Please cite this article as: Parisa Ghasemiyeh, Kiarash Noorizadeh, Dorsa Dehghan, Shiva Rasekh, Ouriel Zadmehr, Soliman Mohammadi-Samani. The Role of Different Factors in Pathophysiology of Acne and Potential Therapeutic Targets: A Brief Review. Trends in Pharmaceutical Sciences. 2022;8(2):107-118. doi: 10.30476/TIPS.2022.95146.1142

Keywords

References

1.    Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015 Sep 17;1:15029. doi: 10.1038/nrdp.2015.29. PMID: 27189872.
2.    Oge' LK, Broussard A, Marshall MD. Acne Vulgaris: Diagnosis and Treatment. Am Fam Physician. 2019 Oct 15;100(8):475-484. PMID: 31613567.
3.    Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):221-5. doi: 10.1016/s0190-9622(86)70025-x. PMID: 2936775.
4.    Downing DT, Strauss JS, Pochi PE. Variability in the chemical composition of human skin surface lipids. J Invest Dermatol. 1969 Nov;53(5):322-7. doi: 10.1038/jid.1969.157. PMID: 5347411.
5.    Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014 May;28(5):527-32. doi: 10.1111/jdv.12298. Epub 2013 Oct 18. PMID: 24134468.
6.    Baldwin H, Tan J. Effects of Diet on Acne and Its Response to Treatment. Am J Clin Dermatol. 2021 Jan;22(1):55-65. doi: 10.1007/s40257-020-00542-y. Erratum in: Am J Clin Dermatol. 2020 Dec 26;: PMID: 32748305; PMCID: PMC7847434.
7.    Nicolaides, N. and T. Ray, Skin lipids. III. Fatty chains in skin lipids. The use ofvernix caseosa to differentiate between endogenous and exogenous components in human skin surface lipid. J Am Oil Chem Soc. 1965 Aug;42:702-7. doi: 10.1007/BF02540043. PMID: 14343880.
8.    Pappas A. Epidermal surface lipids. Dermatoendocrinol. 2009 Mar;1(2):72-6. doi: 10.4161/derm.1.2.7811. PMID: 20224687; PMCID: PMC2835894.
9.    Smith RN, Braue A, Varigos GA, Mann NJ. The effect of a low glycemic load diet on acne vulgaris and the fatty acid composition of skin surface triglycerides. J Dermatol Sci. 2008 Apr;50(1):41-52. doi: 10.1016/j.jdermsci.2007.11.005. Epub 2008 Jan 4. PMID: 18178063.
10.    Wille JJ, Kydonieus A. Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria. Skin Pharmacol Appl Skin Physiol. 2003 May-Jun;16(3):176-87. doi: 10.1159/000069757. PMID: 12677098.
11.    Akaza N, Akamatsu H, Numata S, Matsusue M, Mashima Y, Miyawaki M, Yamada S, Yagami A, Nakata S, Matsunaga K. Fatty acid compositions of triglycerides and free fatty acids in sebum depend on amount of triglycerides, and do not differ in presence or absence of acne vulgaris. J Dermatol. 2014 Dec;41(12):1069-76. doi: 10.1111/1346-8138.12699. Epub 2014 Nov 12. PMID: 25388081.
12.    Stewart ME, Quinn MA, Downing DT. Variability in the fatty acid composition of wax esters from vernix caseosa and its possible relation to sebaceous gland activity. J Invest Dermatol. 1982 Apr;78(4):291-5. doi: 10.1111/1523-1747.ep12507228. PMID: 7069207.
13.    Pappas A, Johnsen S, Liu JC, Eisinger M. Sebum analysis of individuals with and without acne. Dermatoendocrinol. 2009 May;1(3):157-61. doi: 10.4161/derm.1.3.8473. PMID: 20436883; PMCID: PMC2835908.
14.    Ottaviani M, Alestas T, Flori E, Mastrofrancesco A, Zouboulis CC, Picardo M. Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris. J Invest Dermatol. 2006 Nov;126(11):2430-7. doi: 10.1038/sj.jid.5700434. Epub 2006 Jun 15. PMID: 16778793.
15.    Motoyoshi K. Enhanced comedo formation in rabbit ear skin by squalene and oleic acid peroxides. Br J Dermatol. 1983 Aug;109(2):191-8. doi: 10.1111/j.1365-2133.1983.tb07080.x. PMID: 6223652.
16.    Katsuta Y, Iida T, Inomata S, Denda M. Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis. J Invest Dermatol. 2005 May;124(5):1008-13. doi: 10.1111/j.0022-202X.2005.23682.x. PMID: 15854043.
17.    Costa A, Siqueira Talarico A, Parra Duarte Cde O, Silva Pereira C, de Souza Weimann ET, Sabino de Matos L, Della Coletta LC, Fidelis MC, Tannous TS, Vasconcellos C. Evaluation of the Quantitative and Qualitative Alterations in the Fatty Acid Contents of the Sebum of Patients with Inflammatory Acne during Treatment with Systemic Lymecycline and/or Oral Fatty Acid Supplementation. Dermatol Res Pract. 2013;2013:120475. doi: 10.1155/2013/120475. Epub 2013 Sep 26. PMID: 24191156; PMCID: PMC3803126.
18.    Smith KR, Thiboutot DM. Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe? J Lipid Res. 2008 Feb;49(2):271-81. doi: 10.1194/jlr.R700015-JLR200. Epub 2007 Nov 1. PMID: 17975220.
19.    Li WH, Zhang Q, Flach CR, Mendelsohn R, Southall MD, Parsa R. In vitro modeling of unsaturated free fatty acid-mediated tissue impairments seen in acne lesions. Arch Dermatol Res. 2017 Sep;309(7):529-540. doi: 10.1007/s00403-017-1747-y. Epub 2017 May 31. PMID: 28567492.
20.    Melnik BC. Linking diet to acne metabolomics, inflammation, and comedogenesis: an update. Clin Cosmet Investig Dermatol. 2015 Jul 15;8:371-88. doi: 10.2147/CCID.S69135. PMID: 26203267; PMCID: PMC4507494.
21.    Man MQ, Feingold KR, Elias PM. Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin. Arch Dermatol. 1993 Jun;129(6):728-38. PMID: 8507075.
22.    Horrobin DF. Essential fatty acids in clinical dermatology. J Am Acad Dermatol. 1989 Jun;20(6):1045-53. doi: 10.1016/s0190-9622(89)70130-4. PMID: 2526823.
23.    Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):221-5. doi: 10.1016/s0190-9622(86)70025-x. PMID: 2936775.
24.    Stewart ME, Greenwood R, Cunliffe WJ, Strauss JS, Downing DT. Effect of cyproterone acetate-ethinyl estradiol treatment on the proportions of linoleic and sebaleic acids in various skin surface lipid classes. Arch Dermatol Res. 1986;278(6):481-5. doi: 10.1007/BF00455168. PMID: 2947544.
25.    Wertz PW, Miethke MC, Long SA, Strauss JS, Downing DT. The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol. 1985 May;84(5):410-2. doi: 10.1111/1523-1747.ep12265510. PMID: 3158712.
26.    Ziboh VA, Chapkin RS. Biologic significance of polyunsaturated fatty acids in the skin. Arch Dermatol. 1987 Dec;123(12):1686a-1690. PMID: 3688908.
27.    Boxley S. Role of cosmeceutical skincare in the management of acne. J Aesthet Nurs. 2018. 7(Sup1): p. 8-12.
28.    Barros BS, Zaenglein AL. The Use of Cosmeceuticals in Acne: Help or Hoax? Am J Clin Dermatol. 2017 Apr;18(2):159-163. doi: 10.1007/s40257-016-0249-6. PMID: 28063095.
29.    Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK. Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Int J Dermatol. 1995 Jun;34(6):434-7. doi: 10.1111/j.1365-4362.1995.tb04449.x. PMID: 7657446.
30.    Araviiskaia E, Dréno B. The role of topical dermocosmetics in acne vulgaris. J Eur Acad Dermatol Venereol. 2016 Jun;30(6):926-35. doi: 10.1111/jdv.13579. Epub 2016 Feb 24. PMID: 26916232.
31.    Li X, He C, Chen Z, Zhou C, Gan Y, Jia Y. A review of the role of sebum in the mechanism of acne pathogenesis. J Cosmet Dermatol. 2017 Jun;16(2):168-173. doi: 10.1111/jocd.12345. Epub 2017 May 29. PMID: 28556292.
32.    Bakry OA, El Shazly RM, El Farargy SM, Kotb D. Role of hormones and blood lipids in the pathogenesis of acne vulgaris in non-obese, non-hirsute females. Indian Dermatol Online J. 2014 Nov;5(Suppl 1):S9-S16. doi: 10.4103/2229-5178.144506. PMID: 25506579; PMCID: PMC4252966.
33.    Henze C, Hinney B, Wuttke W. Incidence of increased androgen levels in patients suffering from acne. Dermatology. 1998;196(1):53-4. doi: 10.1159/000017867. PMID: 9557226.
34.    Dessinioti C, Katsambas AD. The role of Propionibacterium acnes in acne pathogenesis: facts and controversies. Clin Dermatol. 2010 Jan-Feb;28(1):2-7. doi: 10.1016/j.clindermatol.2009.03.012. PMID: 20082942..
35.    Kumar B, Pathak R, Mary BP, Jha D, Sardana K, Gautam HK. New insights into acne pathogenesis: Exploring the role of acne-associated microbial populations. Dermatologica sin. 2016. 34(2): p. 67-73.
36.    Minegishi K, Aikawa C, Furukawa A, Watanabe T, Nakano T, Ogura Y, Ohtsubo Y, Kurokawa K, Hayashi T, Maruyama F, Nakagawa I, Eishi Y. Complete Genome Sequence of a Propionibacterium acnes Isolate from a Sarcoidosis Patient. Genome Announc. 2013 Jan;1(1):e00016-12. doi: 10.1128/genomeA.00016-12. Epub 2013 Jan 15. PMID: 23405284; PMCID: PMC3556827.
37.    Nakatsuji T, Tang DC, Zhang L, Gallo RL, Huang CM. Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment. PLoS One. 2011 Apr 12;6(4):e14797. doi: 10.1371/journal.pone.0014797. PMID: 21533261; PMCID: PMC3075254.
38.    Mills OH, Criscito MC, Schlesinger TE, Verdicchio R, Szoke E. Addressing Free Radical Oxidation in Acne Vulgaris. J Clin Aesthet Dermatol. 2016 Jan;9(1):25-30. PMID: 26962389; PMCID: PMC4756869.
39.    Konger RL. A new wrinkle on topical vitamin E and photo-inflammation: Mechanistic studies of a hydrophilic gamma-tocopherol derivative compared with alpha-tocopherol. J Invest Dermatol. 2006 Jul;126(7):1447-9. doi: 10.1038/sj.jid.5700308. PMID: 16778813.
40.    Ghasemiyeh P, Mohammadi-Samani S. Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages. Drug Des Devel Ther. 2020 Aug 12;14:3271-3289. doi: 10.2147/DDDT.S264648. PMID: 32848366; PMCID: PMC7429187.
41.    Ghasemiyeh P, Azadi A, Daneshamouz S, Heidari R, Azarpira N, Mohammadi-Samani S. Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting. Pharm Dev Technol. 2019 Sep;24(7):812-823. doi: 10.1080/10837450.2019.1596133. Epub 2019 Apr 26. PMID: 30889371.
42.    Ghasemiyeh P, Azadi A, Daneshamouz S, Mohammadi Samani S. Cyproterone acetate-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): preparation and optimization. Trends in Pharmaceutical Sciences. 2017;3(4):275-86.
43.    Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018 Aug;13(4):288-303. doi: 10.4103/1735-5362.235156. PMID: 30065762; PMCID: PMC6040163.
44.    Rahnama V, Motazedian MH, Mohammadi-Samani S, Asgari Q, Ghasemiyeh P, Khazaei M. Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of in vitro effect on Leishmania major. Res Pharm Sci. 2021 Oct 15;16(6):623-633. doi: 10.4103/1735-5362.327508. PMID: 34760010; PMCID: PMC8562414.
45.    Ghasemiyeh P, Mohammadi-Samani S. Hydrogels as drug delivery systems; pros and cons. Trends in Pharmaceutical Sciences. 2019;5(1):7-24.
46.    Ghasemiyeh P, Mohammadi-Samani S. Polymers Blending as Release Modulating Tool in Drug Delivery. Front Mater. 2021;8:752813. doi: 10.3389/fmats.2021.752813
47.    Castro GA, Ferreira LA. Novel vesicular and particulate drug delivery systems for topical treatment of acne. Expert Opin Drug Deliv. 2008 Jun;5(6):665-79. doi: 10.1517/17425247.5.6.665. PMID: 18532922.
48.    Zouboulis CC, Dessinioti C, Tsatsou F, Gollnick HPM. Anti-acne drugs in phase 1 and 2 clinical trials. Expert Opin Investig Drugs. 2017 Jul;26(7):813-823. doi: 10.1080/13543784.2017.1337745. Epub 2017 Jun 19. PMID: 28627277.
Trends in Pharmaceutical Sciences
Volume 8, Issue 2
June 2022
Pages 107-118

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