From pathogenesis of acne vulgaris to anti-acne agents

Arch Dermatol Res. 2019 Jul;311(5):337-349. doi: 10.1007/s00403-019-01908-x. Epub 2019 Mar 11.

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.

Keywords: Acne; Androgen; Comdogenesis; Cutibacterium acnes; Inflammation; Insulin-like growth factor; Keratinocyte; Sebocyte.

Publication types

  • Review

MeSH terms

  • Acne Vulgaris / etiology
  • Acne Vulgaris / therapy*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Dairy Products / adverse effects
  • Dermatologic Agents / pharmacology
  • Dermatologic Agents / therapeutic use*
  • Dietary Carbohydrates / adverse effects
  • Drug Synergism
  • Humans
  • Propionibacterium acnes / drug effects
  • Propionibacterium acnes / immunology
  • Propionibacterium acnes / isolation & purification
  • Sebaceous Glands / drug effects
  • Sebaceous Glands / immunology
  • Sebaceous Glands / metabolism*
  • Sebum / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Bacterial Agents
  • Dermatologic Agents
  • Dietary Carbohydrates