New Insights Into Systemic Drivers of Inflammation and Their Contributions to the Pathophysiology of Acne

February 2024 | Volume 23 | Issue 2 | 90 | Copyright © February 2024


Published online January 30, 2024

doi:10.36849/JDD.8137

James Del Rosso DOa, Patricia K Farris MDb, Julie Harper MDc, Hilary Baldwin MDd, Adina Hazan PhDe, Isabelle Raymond PhDe

aJDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; Advanced Dermatology and Cosmetic Surgery, Maitland, FL; Department of Dermatology, Touro University Nevada, Henderson, NV
bDepartment of Dermatology, Tulane University School of Medicine, New Orleans, LA
cThe Dermatology and Skin Care Center of Birmingham, Birmingham, AL
dThe Acne Treatment and Research Center, Brooklyn, NY; Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
eNutraceutical Wellness LLC, New York, NY

Abstract


Acne vulgaris (AV) is a prominent skin disease commonly affecting teenagers. It often persists into adulthood and is associated with adverse physical and psychosocial impacts. The pathophysiology of AV is conventionally correlated with 4 factors within and around the pilosebaceous unit: increased sebum production, follicular hyperkeratinization, Cutibacterium acnes proliferation, and localized immune responses. As such, conventional therapeutic approaches for AV have primarily focused on these factors. In addition to this primarily localized pathophysiology, there is a progressively emerging body of evidence indicating that underlying systemic factors contributing to a generalized immuno-inflammatory response can contribute to or exacerbate AV. In this article, we introduce and provide the supporting data, for 6 patient-centric systems that may be implicated in the development of AV: psycho-emotional stress, diet and metabolism, dysbiosis of the gut and skin microbiome, hormonal fluctuations, oxidative stress, and immune response. Identifying these pathways and their contributions in a patient-centric approach may provide expanded therapeutic opportunities for treating patients with AV.

J Drugs Dermatol. 2024;23(2):90-96.   doi:10.36849/JDD.8137

INTRODUCTION

Acne vulgaris (AV) is the eighth most prevalent disease globally, and a condition reported to affect at least 50 million people in the United States.1 Because AV affects 80% of teenagers, it is generally categorized as a condition of adolescence, yet recent literature indicates that AV can affect both pre-teens and adults, with 40%-50% of women experiencing AV that occurs past the teenage years.2-4 Physical and psychosocial sequelae associated with AV include dyschromia, scarring, poor self-image, depression, anxiety, and avoidance of social interaction.5,6 

The pathophysiology of AV is conventionally viewed as resulting from 4 factors occurring at the pilosebaceous unit (PSU): increased sebum, follicular hyperkeratinization, proliferation of Cutibacterium acnes, and inflammation induced by localized immune responses.5 Collectively, this sequence of pathophysiologic events causes marked inflammation in and around the PSU, which results in visible AV lesions and can ultimately lead to both persistent and post-inflammatory hyperpigmentation (PIH) and/or post-inflammatory erythema (PIE) and various forms of scarring.7 

However, there is emerging evidence that many dermatologic conditions are associated with generalized underlying immune-inflammatory systemic responses. Psoriasis, once viewed and treated only as a skin disease, is now accepted as a systemic, inflammatory disease managed primarily by immunomodulatory therapies.8 Atopic dermatitis is now approached, based on scientific evidence, as a disorder driven by a variety of pathways of inflammation, both systemic and cutaneous.9 Hair loss and thinning, once thought of as primarily having local pathogenesis, is now accepted as a multi-factorial systemic condition with more similarities than differences across the hair loss disorder spectrum.10

Likewise, evidence now suggests that the localized pathophysiology of AV is not an isolated event but may be induced or exacerbated by an interconnected web of external and internal stressors propagated by various inflammatory signaling pathways.5 Therefore, an important question to address is what systemic drivers are likely to directly contribute to the pathophysiologic development of AV occurring within and around the PSU. If we can address this question, we might then develop and provide a wider range of therapeutic options.