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From pathogenesis of acne vulgaris to anti-acne agents

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Abstract

Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes (C. acnes) and inflammation. The main hormones responsible for the development of acne vulgaris include androgens, insulin and insulin-like growth factor-1. Other factors involved in this process are corticotropin-releasing hormone, α-melanocyte-stimulating hormone and substance P. Wnt/β-catenin signaling pathway, phosphoinositide 3-kinase (PI3K)/Akt pathway, mitogen-activated protein kinase pathway, adenosine 5′-monophosphate-activated protein kinase pathway and nuclear factor kappa B pathway participate in the modulation of sebocyte, keratinocyte and inflammatory cell (e.g. lymphocytes, monocytes, macrophages, neutrophils) activity. Among all the triggers and pathways mentioned above, IGF-1-induced PI3K/Akt/Forkhead box protein O1/mammalian target of rapamycin (mTOR) C1 pathway is the most important signaling responsible for acne pathogenesis. Commonly used anti-acne agents include retinoids, benzoyl peroxide, antibiotics and hormonal agents (e.g. spironolactone, combination oral contraceptive and flutamide). New approaches including peroxisome proliferator-activated receptor γ modifier, melanocortin receptor antagonists, epigallocatechin-3-gallate, metformin, olumacostat glasaretil, stearoyl-CoA desaturase inhibitor omiganan pentahydrochloride, KDPT, afamelanotide, apremilast and biologics have been developed as promising treatments for acne vulgaris. Although these anti-acne agents have various pharmacological effects against the diverse pathogenesis of acne, all of them have a synergistic mode of action, the attenuation of Akt/mTORC1 signaling and enhancement of p53 signal transduction. In addition to drug therapy, diet with no hyperglycemic carbohydrates, no milk and dairy products is also beneficial for treatment of acne.

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  1. Department of Dermatology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People’s Republic of China

    Tian-Xin Cong, Dan Hao, Xiang Wen, Xiao-Hua Li & Xian Jiang

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People’s Republic of China

    Gu He

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Cong, TX., Hao, D., Wen, X. et al. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res 311, 337–349 (2019). https://doi.org/10.1007/s00403-019-01908-x

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