In this article, we use a systems-wide perspective to identify 6 relevant associations serving as contributory factors of systemic inflammation that may promote the development and/ or augment the severity of AV. These include psycho-emotional stress, an unbalanced diet and metabolism, dysbiosis of the gut and skin microbiome, hormonal fluctuations, oxidative stress, and immune response. Many of these factors have long been cited as playing a role in AV through personal observation or case reports. Presently, clinical and mechanistic evidence suggests the involvement of these factors in the pathophysiology and severity of AV.5,11 Below, we review the current literature supporting these systemic stressors and how they may drive AV lesion formation.
MATERIALS AND METHODS
Systems-Wide Pathophysiology of Acne Vulgaris
The pathophysiology of AV, whether talking about local or systemic cascades that contribute to AV lesion formation or their sequelae, begins and ends with the presence of inflammation, which is subclinical prior to the onset and after the visible resolution of active (palpable) AV lesions.5,12 Our conventional approach to AV management, whether using topical and/or systemic medications, has been to target the 4 major pathophysiologic mechanisms that correlate with the development of AV lesions: follicular hyperkeratosis (microcomedo formation), C. acnes proliferation, increased sebum, and inflammation resulting from local immune responses.12 Over time, publications on AV added to the importance of skin care and exogenous agents, and in more recent years, other considerations such as diet and the microbiome have emerged in the literature.13-17
From the time benzoyl peroxide was discovered for AV in the 1960s, we had little information beyond data on how medications for AV worked until more recently.18 In addition, more attention is being paid to development of approaches to AV management that limit or avoid antibiotic use due to the emergence of antibiotic resistance, which has widespread implications.19,20
In this article, the authors conceptualize beyond just the correlation of how individual medications modify pathways of AV lesion formation. Instead, a broader view of the individual affected by AV is taken, with consideration of other underlying factors that are believed to contribute to a systemic imbalance or dysregulation, all of which provide their contribution to the development of AV. Figure 1 conceptualizes 6 patient-centric factors noted to play a role in a systemic imbalance, and depicts their suggested connection to the underlying inflammation seen in AV.
The Skin Response to Psychological Stress
AV flares are often reported in association with increased stress.21-23 Stress is a triple-edged sword in people with AV. It can contribute to the development of AV flares, it increases after a flare of AV, and/or "hangs overhead like a dark cloud" as many
