Current Concepts in Acne Pathogenesis: Pathways to Inflammation
Multiple mechanisms of IGF-1 may promote the development of acne. IGF-1 has been shown to: (1) induce androgen synthesis and increase the cutaneous availability of dihydrotestos- terone; (2) disinhibit the forkhead box O1 (FoxO1) transcription factor, which normally suppresses the androgen receptor; and (3) activate peroxisome proliferator-activated receptor–gamma, liver X receptor–alpha, and sterol regulatory element binding protein-1c (SREBP-1c). The latter actions increase sebum triglycerides and fatty acid desaturation, leading to a proinflammatory and comedogenic monosaturated fatty acid profile.6 Increased sebum production also leads to increased levels of squalene. Squalene monohydroperoxide is comedogenic and results from ultraviolet A–triggered photooxidation of squalene in sebum.7
Compelling evidence on the roles of hyperglycemic carbohydrates (high glycemic index), dairy products, and saturated fats in promoting acne has been reported.6 Refined carbohydrates and dairy products lead to disinhibition of FoxO1 and activation of the mechanistic target of rapamycin complex 1 (mTORC1) through escalation of insulin and IGF-1 levels. Saturated fats directly activate mTORC1. The effect of the latter is stimulation of SREBP-1c, which is central to sebaceous lipogenesis, sebum fatty acid production, and monosaturation.2,6
Diet-mediated changes in sebum quantity and composition promote P acnes overgrowth and biofilm formation. P acnes produces triglyceride lipase, which increases levels of free palmitic and oleic acids. Palmitic acid, along with P acnes–derived damage-associated molecular patterns, stimulates toll-like receptor 2 (TLR2), thereby triggering inflammasome activation and IL-1– beta signaling. Oleic acid stimulates P acnes adhesion, keratinocyte proliferation, and IL-1–alpha release.8-10 Furthermore, oleic acid can induce formation of comedones (Figure).6,11,12
Acne and Rosacea: Applying Emerging Science to Improve Outcomes
This journal supplement is intended for dermatologists, nurse practitioners, nurses, physician assistants, and other clinicians who treat acne and rosacea.
Supported by an educational grant from:
Bayer
Activity Information
Original Release Date: June 2018
Expiration Date: June 30, 2020
Estimated Time to Complete Activity: 2.0 hours
Faculty
 | Linda F. Stein Gold, MD, Chair |
 | Julie C. Harper, MD |
 | Andrew F. Alexis, MD, MPH |
 | Jerry K. L. Tan, MD, FRCPC |
Method of Participation
Participants should read the activity information, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it out at that time. The online post-test and evaluation can be accessed at http://tinyurl.com/acnerosaceasupp2018. Inquiries about CME accreditation may be directed to the University of Louisville Office of Continuing Medical Education & Professional Development (CME & PD) at [email protected] or (502) 852-5329.
Accreditation Statements
Physicians
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Louisville Global Academy for Medical Education, LLC. The University of Louisville is accredited by the ACCME to provide continuing education for physicians.
The University of Louisville Office of Continuing Medical Education & Professional Development designates this live activity for a maximum of 2.0 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Nurses:
Joint Accreditation Statement
In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and Global Academy for Medical Education. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Continuing Nursing Education
The maximum number of hours awarded for this Continuing Nursing Education activity is 2.0 contact hours.
Designated for 0.6 contact hours of pharmacotherapy credit for Advance Practice Registered Nurses.
Educational Needs
Acne and rosacea are common skin conditions that, if inadequately treated, can significantly affect an individual’s quality of life. Clinicians need tostay current on recent scientific research that is revealing the underlying pathophysiology of these conditions, because such knowledge can support the choice of appropriate therapy to improve outcomes. Inflammation is now known to be a primary factor in acne and may persist throughout the lesion life cycle, even beyond the disappearance of visible lesions. Proliferation of Propionibacterium acnes bacteria contributes to the inflammatory process; the cytokines activated by P acnes infection have been identified as targets for acne therapy, including the use of new and emerging topical and systemic agents. Clinicians should be familiar with new data on traditional, novel, and emerging therapies for rosacea, their mechanisms of action, and their efficacy and safety as monotherapy and in combination. Clinicians should also be familiar with acne treatment strategies targeted for special populations, including adult women (especially those who are or want to become pregnant) and in individuals with skin of color.
Learning Objectives
By reading and studying this supplement, participants should be better able to:
- Design a comprehensive treatment plan for patients with acne based on clinical guidelines and updated research, incorporating pharmacologic and physical modalities
- Discuss and design treatment plans for patients of color, pregnant patients, and those with truncal acne, scarring, and photoaging
- Recognize the significant impact of acne in patients’ lives, and of treating promptly and appropriately
- Apply treatment strategies, based on knowledge of the indications, efficacy, and risks of available rosacea therapies, to achieve therapeutic goals in rosacea treatment
Disclosure Declarations
Individuals in a position to control the content of this educational activity are required to disclose: 1) the existence of any relevant financial relationship with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients with the exemption of non-profit or government organizations and non-health care related companies, within the past 12 months; and 2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.
Andrew F. Alexis, MD, MPH, Consultant: Allergan plc, BioPharmX, Inc., Galderma Laboratories, L.P. Contracted Research: Allergan plc, BioPharmX, Inc., Galderma Laboratories, L.P., Novan, Inc.
Julie C. Harper, MD, Consultant: Allergan plc, Bayer AG, BioPharmX, Inc., Galderma Laboratories, L.P., La Roche-Posay, Novan, Inc., Ortho Dermatologics. Contracted Research: Bayer AG. Speakers Bureau: Allergan plc, Bayer AG, La Roche-Posay, Ortho Dermatologics.
Linda F. Stein Gold, MD, Consultant: Allergan plc, Dermira, Inc., Foamix Pharmaceuticals Ltd., Galderma Laboratories, L.P., Medimetriks Pharmaceuticals, Inc., Novan, Inc., Valeant Pharmaceuticals International, Inc. Contracted Research: Allergan plc, Dermira, Inc., Foamix Pharmaceuticals Ltd., Galderma Laboratories, L.P., Novan, Inc., Valeant Pharmaceuticals International, Inc. Speakers Bureau: Allergan plc, Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc.
Jerry K. L. Tan, MD, FRCPC, Consultant: Allergan plc, Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc. Contracted Research: Dermira, Inc., Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc. Speakers Bureau: Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc.
University of Louisville CME & PD Advisory Board and Staff Disclosures: The CME & PD Advisory Board and Staff have nothing to disclose.
CME/CE Reviewers: Cindy E. Owen, MD, Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of Louisville School of Medicine, has nothing to disclose. The Postgraduate Institute of Medicine planners and managers have nothing to disclose.
Global Academy for Medical Education Staff: Eileen A. McCaffrey, MA; Tristan M. Nelsen, MNM, CMP, HMCC; Sylvia H. Reitman, MBA, DipEd; and Ron Schaumburg have nothing to disclose.
Off-Label/Investigational Use Disclosure
This CME/CE activity discusses the off-label use of certain approved medications as well as data from clinical trials on investigational agents. Any such material is identified within the text of the articles.
Contact Information for Technical Questions
Please technical questions or concerns to Global Academy for Medical Education at 973-290-8225 or email [email protected].
Copyright Statement
Copyright © 2018 by Global Academy for Medical Education, LLC, Frontline Medical Communications Inc., and its Licensors. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. Global Academy for Medical Education, LLC, Global Education Group, and Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.
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- Fitz-Gibbon S, Tomida S, Chiu BH, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133:2152-2160.
- Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32:23-63.
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- Janiczek-Dolphin N, Cook J, Thiboutot D, Harness J, Clucas A. Can sebum reduction predict acne outcome? Br J Dermatol. 2010;163:683-688.
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- Qin M, Landriscina A, Rosen JM, et al. Nitric oxide-releasing nanoparticles prevent Propionibacterium acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response. J Invest Dermatol. 2015;135:2723-2731.
- Baldwin H, Blanco D, McKeever C, et al. Results of a phase 2 efficacy and safety study with SB204, an investigational topical nitric oxide-releasing drug for the treatment of acne vulgaris. J Clin Aesthet Dermatol. 2016;9:12-18.
- Rocha MAD, Guadanhim LRS, Sanudo A, Bagatin E. Modulation of toll like receptor-2 on sebaceous gland by the treatment of adult female acne. Dermatoendocrinol. 2017;9:e1361570.
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- Dispenza MC, Wolpert EB, Gilliland KL, et al. Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. J Invest Dermatol. 2012;132:2198-2205.
- Gregoriou S, Kritsotaki E, Katoulis A, Rigopoulos D. Use of tazarotene foam for the treatment of acne vulgaris. Clin Cosmet Investig Dermatol. 2014;7:165-170.
- Tenaud I, Khammari A, Dreno B. In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol. 2007;16:500-506.
- Zuliani T, Khammari A, Chaussy H, Knol AC, Dréno B. Ex vivo demonstration of a synergistic effect of adapalene and benzoyl peroxide on inflammatory acne lesions. Exp Dermatol. 2011;20:850-853.
- Jones DA. Rosacea, reactive oxygen species, and azelaic acid. J Clin Aesthet Dermatol. 2009;2:26-30.
Disclosures
Publication of this CME/CE article was jointly provided by University of Louisville, Postgraduate Institute for Medicine, and Global Academy for Medical Education, LLC, and is supported by an educational grant from Bayer. The authors have received an honorarium for their participation in this activity. They acknowledge the editorial assistance of Eileen A. McCaffrey, MA, medical writer, and Global Academy for Medical Education in the development of this continuing medical education journal article.
Jerry K. L. Tan, MD, FRCPC, Consultant: Allergan plc, Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc. Contracted Research: Dermira, Inc., Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc. Speakers Bureau: Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc.
Linda F. Stein Gold, MD, Consultant: Allergan plc, Dermira, Inc., Foamix Pharmaceuticals Ltd., Galderma Laboratories, L.P., Medimetriks Pharmaceuticals, Inc., Novan, Inc., Valeant Pharmaceuticals International, Inc. Contracted Research: Allergan plc, Dermira, Inc., Foamix Pharmaceuticals Ltd., Galderma Laboratories, L.P., Novan, Inc., Valeant Pharmaceuticals International, Inc. Speakers Bureau: Allergan plc, Galderma Laboratories, L.P., Valeant Pharmaceuticals International, Inc.
Andrew F. Alexis, MD, MPH, Consultant: Allergan plc, BioPharmX, Inc., Galderma Laboratories, L.P. Contracted Research: Allergan plc, BioPharmX, Inc., Galderma Laboratories, L.P., Novan, Inc.
Julie C. Harper, MD, Consultant: Allergan plc, Bayer AG, BioPharmX, Inc., Galderma Laboratories, L.P., La Roche-Posay, Novan, Inc., Ortho Dermatologics. Contracted Research: Bayer AG. Speakers Bureau: Allergan plc, Bayer AG, La Roche-Posay, Ortho Dermatologics.
Address reprint requests to: Jerry K. L. Tan, MD, FRCPC, Schulich School of Medicine & Dentistry, Western University, 2224 Walker Road,
Suite 300, Windsor, Ontario, N8W 5L7 Canada; [email protected]
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