R E V I E W A RT I C L E
Summary
Correspondence
Ketaki Bhate.
E-mail: ketaki.bhate@nottingham.ac.uk
Funding sources
None.
Conicts of interest
None declared.
DOI 10.1111/bjd.12149
The clinical and histological features of acne, a chronic inflammatory disease of the pilosebaceous unit, are well described.1
Acne lesions are typically classified as noninflammatory (open
and closed comedones) or inflammatory (papules and pustules). Seborrhoea, or grease production, is also a feature.2
Scarring is often present following inflammation3 as illustrated
in Figure 1. The pathophysiological events occurring in acne
are also relatively well studied. Lesions start when keratinocytes lining the hair follicle desquamate creating a microcomedone. At puberty increased sebum production creates an
environment that can sustain the colonization of Propionibacterium acnes. As P. acnes proliferates, inflammatory and chemotactic
mediators are produced, which in turn drive inflammatory
processes.4
Despite advances in understanding the pathophysiology of
acne, much less appears to have been written about its epidemiology, which is strange considering that acne is almost
universal in teenage years. Epidemiology not only describes
the burden of disease in terms of incidence, prevalence and
Similarly, we did not attempt any meta-analysis given the variation in study design and outcomes, although we have
attempted to provide summative descriptive comments for
each aspect of the field. Meta-analysis was also compromised
by the high degree of variability in the outcome measures
employed by our included studies, including photonumeric
scores, lesion counts and patient-assessed scores, many of
which have not been tested for reliability or validity as has
been highlighted elsewhere.10
Search methods
We searched the Medline database (in process and other nonindexed citations and Ovid Medline 1946present) and Embase from 1974 until the end of November 2011.
Additionally, NHS evidence, a collection of filtered resources
for the U.K. National Health Service, was searched. Our search
strategy involved several separate searches for each section,
combining the terms acne vulgaris with: epidemiology, aetiology, cause, prevalence, incidence, cost, pharmacoeconomics,
socioeconomic, social, natural history, race, ethnicity, morbidity, quality of life, geography, family size, severity, excoriation, obesity, overweight, pathogenesis, washing, sweat,
cleanse, sun, sunlight, light, diet, dairy, milk, glycaemic glycemic index (GI), GI, high GI, chocolate, hygiene, smoking,
prevention, climate, environment, infection, Propionibacterium acnes, stress, picking, chloracne, drugs and medicine. The function of truncation in the Ovid search engine to expand upon
suffixes was employed. In order to make the search as wide as
possible, additional limits such as study type were not applied.
There were no prespecified criteria for study inclusion or
exclusion and there was no time limit to which studies
included in this review dated back to. Additional articles were
identified from citations retrieved from electronic bibliographic searching. Our aim was to provide a review that covered all aspects of what could be considered as acne
epidemiology in one succinct article. We did not prespecify
any particular study type given the wide scope of this review.
Although we comment on the quality of evidence for key individual studies, we did not undertake any formal grading of
the quality of evidence given the large diversity of study types.
2012 The Authors
BJD 2012 British Association of Dermatologists 2013 168, pp474485
Socioeconomic impact
A large cohort study in Canada found that those of low socioeconomic background were referred less to dermatologists
than those of a higher socioeconomic background and, additionally, those in rural areas were referred less than those
based in urban areas.53 Interestingly, a cross-sectional study
from Saudi Arabia found acne to be more prevalent in high
socioeconomic classes.54 A Texan study of adolescents with a
low socioeconomic background found those with acne
reported lower self-esteem.55 Studies have shown that patients
with acne have a higher rate of unemployment than matched
controls.56 In the U.S.A., over 3 billion dollars per year is lost
in the direct and indirect costs of treatment and loss of productivity.57 The presence of acne has been reported to have a
negative effect upon work school performance.58 Unemployment rates were compared in 625 patients with acne and 625
controls and were higher in the group of patients with acne,
although social status and academic background were not con-
Genetics
The risk factors and genes associated with acne prognosis
remain unclear.61 A large study of Chinese undergraduates
found acne to have a 78% heritability in first-degree relatives15 and other population-based studies have concurred.34
Acne occurs earlier and is more severe in those with a positive
family history.34,61 Several retrospective twin studies have
found a possible genetic basis with familial clustering.6266
More recently, a prospective twin study comparing monozygotic and dizygotic twins found that acne severity was genetically determined, although the low power of the study could
not rule out the influence of additional environmental factors.67 Twin studies in acne are summarized in Table 1 and
highlight the need for a further large, twin-based prospective
study and subsequent further molecular genetic analyses.
Ethnicity
Frequency in different ethnic groups
In 1908, Fox68 reported that 74% (163 2200) of caucasian
patients and 46% (101 2200) of black patients had acne vulgaris. Hazen69 in 1914 found a similar frequency of acne in
2000 outpatient visits of black patients when compared with
2000 caucasian patients (84% and 9%, respectively). Such
clinic-based studies are not a good method of making inferences about population characteristics as the estimates could
reflect selection bias in those attending or differences in diagnostic perception.
Conversely, Cheng et al.70 found that on a scale of never,
rarely, sometimes, often and always, white individuals
have an increased risk of developing acne frequency compared
with nonwhites, particularly black subjects (n = 1214). Given
this was a questionnaire-based study it is also susceptible to
selection bias. There have been many other similar studies,
some finding acne between black and white individuals to be
similar in prevalence incidence and others finding a slight discrepancy. There are relatively few comparative surveys
between ethnic groups, studies in the literature tending to
conclude that acne is one of the more common skin conditions in the ethnic group under review.71,72 Freyre et al.73
conducted a cross-sectional study in Peru of 2214 subjects
aged between 12 and 18 years who were either Mestizo,
Indian or white. They found the prevalence of acne in Indians
was significantly less (2797%) than in Mestizos (4308%) or
whites (4447%). Again, there is an element of selection bias
2012 The Authors
BJD 2012 British Association of Dermatologists 2013 168, pp474485
66
Prospective
transverse
study
Cross-sectional
Prospective
longitudinal
Sobral-Filho
et al.65
Bataille
et al.62
Evans et al.67
Women and men. Unclear if
they had pre-existing acne
Participants
458 monozygotic
twins, 1099
dizygotic twins
778 twin pairs.
Unclear proportions
of monozygotic
vs. dizygotic
200 pairs,
monozygotic and
dizygotic
40 pairs of twins:
20 identical,
20 nonidentical
(?mono and
dizygotic)
Sample size
Measurement
of serum
excretion
and acne
grades
Retrospective
case-note
analysis
Retrospective
case-note
analysis
Design
Walton
et al.64
Friedman63
Niermann
Study
Main findings
Of retrospective design
Limitations
Diet
Historically, dietary advice was commonplace as part of acne
therapy. Because early studies hinted that patients with acne
had impaired glucose tolerance and altered carbohydrate
metabolism, patients were advised to avoid excessive carbohydrate and sugary foods.87,88
In 1971 Anderson studied 27 students who consumed a
high-carbohydrate diet and found there were no flares in acne
over the study period. The lack of a control group and small
Chocolate
There is a well-recognized belief that chocolate causes or exacerbates acne, particularly among adolescents.110,111 There is,
however, limited evidence backing up such a claim. Two very
small earlier studies had such methodological shortcomings
that it was difficult to draw any conclusions89,112 (Table 2). In
1975 a single-blind, placebo-controlled, crossover trial in 65
male prisoners found there to be no difference in acne severity
between a chocolate-eating group and a chocolate-abstinent
group. This study also had major methodological flaws: methods of randomization were not described and blinding was
only partly described, and there was a high risk of bias as there
was no intention-to-treat analysis performed.89 More recently,
a small, nonrandomized, uncontrolled study of 10 people
found a significant increase in acneiform lesions upon consumption of chocolate made up of 100% cocoa.113 The question of whether chocolate worsens acne therefore remains
unanswered and there is much controversy and speculation
especially among adolescents who frequently turn to doctors
for advice. Such paucity of evidence highlights a clear need for
a well-designed, blinded, randomized, provocation trial.
Sunlight
Various authors have debated whether ultraviolet radiation or
visible light worsens, improves or has no effect upon acne
vulgaris. A systematic review of seven studies found no
Study
Design
Participants
Main findings
Limitations
Grant and
Anderson112
Uncontrolled
provocation
study
Anderson89
Uncontrolled
provocation
study
Fulton et al.90
Single blind,
placebocontrolled
crossover,
randomized
University
students. Mild
to moderate
acne
University
students with
acne who
claimed that
certain food
exacerbated
their acne
Male prisoners
65
No difference in acne
severity between the two
groups
10
Berman et al.113
Interventional,
uncontrolled.
100% chocolate
consumed
Men
Unknown
Hygiene
Smoking
Whether or not acne is caused by, exacerbated, improved,
cured, or is not associated with smoking remains controversial.31,125130 An earlier case series suggested an inverse relationship between acne and smoking, suggesting an antiinflammatory effect of a component found in cigarettes.125
Obesity
Infection
The exact role of bacteria such as P. acnes in the pathogenesis
of acne vulgaris is subject to much speculation. Propionibacterium
acnes was first implicated in acne pathogenesis in 1896 when
the microorganism found in acne lesions was thought to be
the main cause of acne; this was supported by another study
in 1909.147,148 Despite this, laboratory studies showed that
the number of P. acnes in the skin of patients with acne and
controls without acne was the same and there was no increase
in P. acnes number in severe acne vs. mild moderate acne,
prompting the suggestion that P. acnes was a secondary colonizer of the anaerobic lipid-rich environment, rather than a
primary pathogen.149151 A large, randomized controlled trial
comparing five antimicrobial regimens noted that clinical efficacy of oral antibiotics was less in those with resistant strains,
suggesting that antibiotics may work through a direct antimicrobial as well as anti-inflammatory effect. This is a concept
that the majority of experimental studies have supported,
although not all.152155 Similar bacterial resistance has been
seen in other studies as well,156,157 and in vitro experiments
have shown that resistance may be due to the formation of
biofilms.158 There have been several other postulated mechanisms in which P. acnes is directly involved in acne pathogenesis, for example, the interaction of P. acnes and Toll-like
receptors involved in signalling of the innate and adaptive
immune response and the subsequent production of proinflammatory cytokines; however, the exact mechanism has not
been confirmed. Pathway targets have been used for experiments into possible vaccine development.159,160 Conversely,
the authors of a recent literature review collating evidence of
P. acnes and it relationship to the pathogenesis of acne concluded that P. acnes was unlikely to have an active role in the
development of inflammatory noninflammatory acne lesions.161 How and if P. acnes influences the development of
and perpetuation of acne lesions remains unclear at this stage.
Interestingly, acne is not described in other animals apart from
comedonal chin acne in cats and dogs, which is probably
another entity.162,163 Given that animals do develop comedones and that their pilosebaceous units are under the control of
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BJD 2012 British Association of Dermatologists 2013 168, pp474485
Conclusions
Despite many attempts at investigating the epidemiology of
acne, few studies have provided any clear answers. Observational studies, while useful at generating hypotheses, have
been generally limited by traditional drawbacks such as information bias, confounding, reverse causation and the lack of
suitable controls. Future observational studies need to distinguish between those factors that may be associated with the
first appearance of acne and those with an effect upon severity, which would thereby influence treatment. The evidence of
dietary factors in acne requires closer examination in cohort
and experimental studies and the development of a universal
grading system is required to facilitate further meta-analytical
work in all aspects of acne epidemiological work. Additionally, there is a paucity of longitudinal studies looking into the
natural history of acne and the various steps in the processes
leading to colonization with P. acnes. Such studies may identify
potential merit in the treatment of acne prepubertally with a
view to altering the natural history of P. acnes colonization and
subsequent inflammatory acne.
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