INTRODUCTION
Two primary factors are changing current approaches
to the management of acne vulgaris (AV): the continuously
evolving role of Propionibacterium acnes in the
pathophysiology of AV and emerging evidence of an inflammatory
basis for AV. The developing concepts emphasize that
acne is primarily an inflammatory disease. Recent research has
confirmed that inflammation is the hallmark of all acne lesions,
from the microcomedo to so-called “noninflammatory” lesions
(open and closed comedones), to inflammatory lesions (papules,
pustules, nodules, and "cysts"), to “postinflammatory”
erythema and hyperpigmentation and scarring.
The pathophysiology of acne and associated scarring were
elucidated with reports of marked elevations in inflammatory
cytokine gene transcripts in active acne lesions, including tumor
necrosis factor (TNF)-α and interleukin (IL)-1β, leading to
an amplification of nuclear factor (NF)-kB signaling pathways.
There were also significant increases in IL-8 and IL-10 and elevated
activator protein (AP)-1 in acne lesions. This leads to
elevated matrix metalloproteinases, which degrade collagen up
to 2.5 fold compared with normal skin. Moreover, this inflammatory
process was localized to the pilosebaceous unit.1
Given these findings, clinicians are re-evaluating their therapeutic
targets in the pathogenesis of AV and exploring optimal
regimens that reduce inflammation without contributing to
antibiotic resistance.
A History of Inflammation
There was no doubt that inflammation played an important role
in the development of inflammatory lesions, such as papules
and pustules, or that P. acnes played a role leading to secondary
inflammatory processes in those stages of acne development.
Recent research has elucidated the role of inflammation in the
pathogenesis of acne and, more precisely, the contribution of P. acnes to drive inflammation.1-9 It was already well established
that acne is not an infectious process.2 P. acnes is now shown
to drive the inflammation of AV via various different pathways
throughout the course of the disease process, one of the most
important is via the activation of innate immunity.3 P. acnes is
thought to instigate an inflammatory cytokine response via
activation of toll-like receptor (TLR)-2,3 which triggers a proinflammatory
cytokine pattern.1-7
However, we are now discovering that subclinical inflammation
is present at the onset of disease and it is not only driven
by P. acnes. Studies by Jeremy et al and others have shed light
on the concept of early preclinical inflammation in acne8 that
typically persists throughout the acne lesion life cycle.6-7 They
have documented a prelesional folliculocentric inflammatory
phase of acne, evidenced by markedly increased numbers of
CD4+ T lymphocytes; numbers of macrophages; upregulated
expression of perifollicular IL-1; and upregulation of epidermal
expression of α-integrins. These mediators are elevated in
both normal skin and early papules of subjects with acne compared
with normal skin of subjects without acne. Additionally,
in subjects with acne, lesions had increased inflammatory
mediators relative to uninvolved skin. Those mediators are
also part of the immune system activation. More importantly,
they were able to show that prelesional inflammation
preceded follicular hyperkeratinization and the presence of
microcomedones.8 These findings suggest that the so-called
