Overview of the Pathogenesis of Acne (1)

INTRODUCTION
Acne is an extremely complex disease with elements of pathogenesis involving
defects in epidermal keratinization, androgen secretion, sebaceous function,
bacterial growth, inflammation, and immunity. In the past 30 years, much has
been worked out, and we now have a fairly detailed understanding of the events
that result in an acne pimple, although there is also much left to be discovered.
COMEDO FORMATION
The initial event in acne is the formation of comedo, a plug in the follicle, which is
termed “open” if a black tip is visible in the follicular orifice and “closed” if the
opening has not distended enough to be visible without magnification. Patients
(and their mothers) erroneously conclude that this black tip is due to dirt in the
follicle. Rather, it represents oxidized melanin and perhaps certain sebaceous
lipids (1,2). The earliest lesion is termed microcomedo and is clinically inapparent,
but is the lesion that gives rise to inflammatory acne. Microcomedones are best
visualized by harvesting them using cyanoacrylate glue (3). By this method, micro-
comedones are seen to be numerous on the skin of acne patients, and much less
prevalent and less robust on the skin of normal individuals.
Comedo formation begins with faulty desquamation of the follicular lining.
Instead of shedding as fine particles, the epithelium comes off in sheets that are
incapable of exiting through the follicular orifice, and hence a plug results. Con-
centric laminae of keratinous material fill and distend the follicle. This process is
first detectable at the junction of the sebaceous duct and the follicular epithelium
and involves in distal cells later. The granular layer becomes prominent, tono-
filaments increase, and lipid inclusions form the desquamated keratin (1,4).
Most comedones contain hairs, usually small vellus hairs, and the age of a
comedo may be reflected by the number of hairs that it contains (5). Terminal
hairs are almost never seen in comedones. It may be that the presence of a stout
hair in the follicle provides a mechanical opening that prevents comedo distention.
Is it possible that the conversion of vellus to terminal hairs as acne patients mature
is the explanation for the decrease in acne in the late teens and early 20s?
The cause of the faulty desquamation that leads to comedo formation is not
known. Comedones have been demonstrated before puberty, so activation of sebac-
eous secretion cannot be the key event (1). Many compounds have been shown to
induce comedones in experimental systems (e.g., coal tar, sulfur, squalene, haloge-
nated biphenyls, and cutting oils), but none are obviously relevant to the natural
course of acne formation (6–8). Two experimental systems exist for studying
comedo formation: the rabbit ear model and the backs of human volunteers.
In general, the rabbit ear is more sensitive and forms plugs easily, but there is
generally good agreement between the two systems for most compounds (6–8).
Physical agents may also enhance comedogenesis. Favre–Racouchaut syn-
drome consists of severe photodamage accompanied by open comedones on the
face (9). Mills et al. (10,11) have demonstrated that UV irradiation will enhance
the comedo formation in the rabbit ear engendered by squalene, cocoa butter,
sebum, and some sunscreens.
Inflammation may also play a role in the formation of comedones. A ring of
comedones may be occasionally seen around a large inflammatory nodule on the
back of patients with severe acne. In vitro studies have shown that Propionibacterium
acnes cell walls will induce follicular plugging in proportion to the degree of inflam-
mation triggered by bacteria in the skin of rats (12). More recent studies in an in
vitro model of the acne follicle show that cytokines such as interleukin (IL)1-a
modulate the cornification of the epidermis and may be involved in the inflamma-
tory induction of comedones (13,14).
Another potential cause of comedo formation is the lipid contents of the fol-
licle itself. Bacterial lipolysis will liberate fatty acids from sebaceous triglycerides
that are comedogenic, but the presence of microcomedones in the skin of prepuber-
tal children (who have no follicular microflora and no sebum) argues against a
major role of bacterial action in early comedogenesis (15). Strauss et al. (16) have
shown that the sebum of acne patients is relatively deficient in linoleic acid,
perhaps reflective of high sebum secretion rates and have suggested that local
linoleic acid deficiency may be involved in comedo formation. Further study of
this possibility is warranted.