Evolving Perspectives on the Etiology and Pathogenesis of Acne Vulgaris

March 2015 | Volume 14 | Issue 3 | Original Article | 263 | Copyright © March 2015

Lawrence F. Eichenfield MD,1 James Q. Del Rosso DO FAOCD,2 Anthony J. Mancini MD,3
Fran Cook-Bolden MD,4 Linda Stein Gold MD,5 Seemal Desai MD FAAD,6 Jonathan Weiss MD,7
David Pariser MD,8 Joshua Zeichner MD,9 Neal Bhatia MD,10 Leon Kircik MD11

1University of California, Rady Children’s Hospital, San Diego, CA
2Touro University Nevada College of Osteopathic Medicine
3Northwestern University Feinburg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL
4Beth Isreal Medical Center, New York, NY
5Henry Ford Health System, Detroit, MI
6University of Texas Southwestern Medical Center & Innovative Dermatology, Dallas,TX
7PC and Gwinnet Clinical Research Center, Inc., Snellville, GA
8Eastern Virginia Medical School, Norfolk, VA
9Mount Sinai Medical Center, New York, NY
10Therapeutics Clinical Research, San Diego, CA
11Icahn School of Medicine at Mount Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care,
PLLC, Louisville, KY

As the pathophysiology of acne is complex and multifactorial, the continued influx of new basic science and clinical information requires careful analysis before drawing conclusions about what truly contributes to the development and progression of this chronic disease. Our objective is to review the latest evidence and highlight a number of important perspectives on the pathophysiology of acne. An improved understanding of acne pathogenesis should lead to more rational therapy and a better understanding of the role of P acnes opens new perspectives for the development of new treatments and management. Further research may be directed at targeting receptors, adhesion molecules, cytokines, chemokines or other pro-inflammatory targets implicated in the activation of immune detection and response (i.e., toll-like receptors [TLRs], protease-activated receptors [PARs]) that appear to contribute to the pathophysiology of acne. Therapeutic options that reduce the need for topical and/or oral antibiotic therapy for acne are welcome as bacterial resistance to antibiotics is a clinically relevant concern both in the United States and globally.

J Drugs Dermatol. 2015;14(3):263-268.


Acne vulgaris (acne) is the most common skin disorder seen in ambulatory dermatology practices in the United States regardless of gender, skin color or ethnicity.1-3
Its etiology is multifactorial, with several pathophysiologic associations identified, including hormonal function, increased sebum production, follicular hyperkeratinization, proliferation of Propionibacterium acnes (P acnes), and various cascades of inflammation.4 One of the enigmas is why acne often remits in the early twenties, when there is no reduction in the amount of P acnes or sebum production. Evidence now supports a pivotal role for cellular inflammatory events at all stages of acne lesion development, and with recognition of early subclinical acne lesion formation as both follicular hyperkeratinization and inflammatory cellular infiltration. Biomarkers of inflammation function independently and collectively to help drive the progression of acne lesion development, with various inflammatory cascades contributing throughout the “life cycle” of an acne lesion.5 Improvement in acne with therapeutic agents may be due to the inhibition of inflammatory cascades, reduction of follicular hyperkeratinization, and suppression of the effects of androgens.
Although the sequence of events leading to lesion formation has become clearer, possible mechanisms leading to the development of a microcomedone and its transformation into an inflamed lesion remain less clear.6
Many inflammatory pathways and factors are involved in acne pathogenesis; however, the initial inciting stimulus has not been identified. Several exacerbating factors have been suggested including diet, menstruation, sweating, personal stress, ultraviolet radiation, application of pomades and occupation.7 It has been reported that a low glycemic-load diet improves acne, however, this may only be applicable to a subset of patients with a propensity to develop the metabolic syndrome.8 There is some evidence that at least some patients with acne are under increased cutaneous and systemic oxidative stress. The burden of oxidative