The primary role of sebum in the pathophysiology of acne vulgaris and its therapeutic relevance in acne management

Abstract

Background

Sebum physiology and its contributions to acne vulgaris (AV) pathophysiology have been long debated. Within the pilosebaceous unit, androgens drive sebocyte production of sebum, comprising mono-, di-, and triglycerides (the latter converted to fatty acids); squalene; cholesterol; cholesterol esters; and wax esters. Upon release to the skin surface, human sebum has important roles in epidermal water retention, antimicrobial defenses, and innate immune responses.

Aims

Alterations in sebum alone and with other pathogenic factors (inflammation, follicular hyperkeratinization, and Cutibacterium acnes [C. acnes] proliferation) contribute to AV pathophysiology. Androgen-driven sebum production, mandatory for AV development, propagates C. acnes proliferation and upregulates inflammatory and comedogenic cascades.

Results

Some sebum lipids have comedogenic effects in isolation, and sebum content alterations (including elevations in specific fatty acids) contribute to AV pathogenesis. Regional differences in facial sebum production, coupled with patient characteristics (including sex and age), help exemplify this link between sebum alterations and AV lesion formation.

Conclusions

To date, only combined oral contraceptives and oral spironolactone (both limited to female patients), oral isotretinoin and topical clascoterone (cortexolone 17α-propionate) modulate sebum production in patients with AV. A better understanding of mechanisms underlying sebaceous gland changes driving AV development is needed to expand the AV treatment armamentarium.

Keywords:

• Acne vulgaris
• individualized treatment
• pathophysiology
• sebaceous gland
• sebum
• therapeutics

Acknowledgments

Manuscript preparation and editorial support were provided by AlphaBioCom, a Red Nucleus company. This support was funded by Sun Pharma.

Disclosure statement

JDR has served as a research investigator, consultant, and/or speaker for Allergan, Almirall, Amgen (Celgene), Arcutis, Bausch Health (Ortho Dermatologics), Bayer Healthcare Pharmaceuticals, Beiersdorf, Biorasi, Bristol Myers Squibb, Cassiopea, Cutera, Dermavant Sciences, Dr Reddy, Eli Lilly, EPI Health, Evommune, Ferndale, Galderma, JEM Health, Johnson & Johnson, Journey, LEO Pharma, L’Oréal, Mayne Pharma, Novan, Sebacia, Sol-Gel, Sun Pharma, Strata, and Vyne. LK has served as an investigator, speaker, advisory board member, or consultant for 3 M, Abbott, Aclaris Therapeutics, Allergan, Amgen, Anacor Pharmaceuticals, Assos Pharmaceuticals, Astellas Pharma US, Asubio Pharma, Bayer Healthcare Pharmaceuticals, Berlex Laboratories (Bayer Healthcare Pharmaceuticals), Biogen, BioLife, Biopelle, Blue Willow Biologics, Boehringer Ingelheim, Breckenridge Pharmaceutical, Celgene Corporation, Centocor, ColBar LifeScience, CollaGenex Pharmaceuticals, Combimatrix Molecular Diagnostics, Connetics Corporation, Coria Laboratories, Dermik Laboratories, Dermira, Dow Pharmaceutical Sciences, DUSA Pharmaceuticals, Eli Lilly, Embil Pharmaceutical, EOS Pharmaceutical, Ferndale Pharma Group, Galderma, Genentech, GSK, Healthpoint, Idera Pharmaceuticals, Innocutis Medical, Innovail, Johnson & Johnson, Laboratory Skin Care, LEO Pharma, L’Oréal, Maruho, Medical International Technologies, Medicis Pharmaceutical, Merck, Merz Pharma, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals, Obagi Medical Products, Ortho Neutrogena, Pediapharma, Pfizer, PharmaDerm, Promius Pharma, PuraCap Pharmaceutical, QLT, Quatrix, Quinnova Pharmaceuticals, Serono (Merck-Serono International), SkinMedica, Stiefel Laboratories, Sun Pharma, Taro Pharmaceutical Industries, TolerRx, Triax Pharmaceuticals, UCB, Valeant Pharmaceuticals North America, Warner Chilcott, XenoPort, and ZAGE.

Data availability statement

Data sharing is not applicable to this article as no data sets were generated or analyzed during the current study.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.