acne eidemics - k. bhate and h.c. williams

REVIEW ARTICLE

BJD

British Journal of Dermatology

Epidemiology of acne vulgarisK. Bhate and H.C. Williams

Centre of Evidence Based Dermatology, University of Nottingham, Room A103, King’s Meadow Campus, Lenton Lane, Nottingham NG7 2NR, U.K.

CorrespondenceKetaki Bhate.

E-mail: [email protected]

Accepted for publication31 October 2012

Funding sourcesNone.

Conflicts of interestNone declared.

DOI 10.1111/bjd.12149

Summary

Despite acne being an almost universal condition in younger people, relativelylittle is known about its epidemiology. We sought to review what is knownabout the distribution and causes of acne by conducting a systematic review ofrelevant epidemiological studies. We searched Medline and Embase to the endof November 2011. The role of Propionibacterium acnes in pathogenesis is unclear:antibiotics have a direct antimicrobial as well as an anti-inflammatory effect.Moderate-to-severe acne affects around 20% of young people and severity corre-lates with pubertal maturity. Acne may be presenting at a younger age becauseof earlier puberty. It is unclear if ethnicity is truly associated with acne. Blackindividuals are more prone to postinflammatory hyperpigmentation and specificsubtypes such as ‘pomade acne’. Acne persists into the 20s and 30s in around64% and 43% of individuals, respectively. The heritability of acne is almost80% in first-degree relatives. Acne occurs earlier and is more severe in thosewith a positive family history. Suicidal ideation is more common in thosewith severe compared with mild acne. In the U.S.A., the cost of acne is over3 billion dollars per year in terms of treatment and loss of productivity. Asystematic review in 2005 found no clear evidence of dietary componentsincreasing acne risk. One small randomized controlled trial showed that lowglycaemic index (GI) diets can lower acne severity. A possible associationbetween dairy food intake and acne requires closer scrutiny. Natural sunlight orpoor hygiene are not associated. The association between smoking and acne isprobably due to confounding. Validated core outcomes in future studies willhelp in combining future evidence.

The clinical and histological features of acne, a chronic inflam-

matory disease of the pilosebaceous unit, are well described.1

Acne lesions are typically classified as noninflammatory (open

and closed comedones) or inflammatory (papules and pus-

tules). 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 keratino-

cytes lining the hair follicle desquamate creating a microcome-

done. At puberty increased sebum production creates an

environment that can sustain the colonization of Propionibacteri-

um 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 epide-

miology, 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

variations according to age, sex, social class, ethnic group and

geography, but also has the potential to identify specific risk

factors for disease occurrence or progression, which may be

amenable to manipulation. Discovery of risk factors or factors

that exacerbate existing disease could lead to appropriate pri-

mary or secondary preventative measures and treatments,

which in turn could lead to population benefits in terms of

health and reduced expenditure on relatively ineffective treat-

ments. Epidemiology is also concerned with natural history

and progression.5,6

This article seeks to provide a comprehensive review on the

epidemiology of acne vulgaris. The epidemiology of other

forms of acne – acne rosacea, infantile acne and acne inversa

(hidradenitis suppurativa) – are not discussed in this review.7–9

We begin with an overview of the descriptive epidemiology

of acne vulgaris including incidence, prevalence, severity,

morbidity, economics and financial implications, demograph-

ics and natural history. We then move on to possible causative

factors, which in turn lead into possible prevention strategies.

� 2012 The Authors

474 BJD � 2012 British Association of Dermatologists 2013 168, pp474–485

Search methods

We searched the Medline database (in process and other non-

indexed citations and Ovid Medline 1946–present) and Em-

base 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, aetiol-

ogy, cause, prevalence, incidence, cost, pharmacoeconomics,

socioeconomic, social, natural history, race, ethnicity, morbid-

ity, quality of life, geography, family size, severity, excoria-

tion, obesity, overweight, pathogenesis, washing, sweat,

cleanse, sun, sunlight, light, diet, dairy, milk, glycaemic ⁄gly-cemic index (GI), GI, high GI, chocolate, hygiene, smoking,

prevention, climate, environment, infection, Propionibacterium ac-

nes, stress, picking, chloracne, drugs and medicine. The func-

tion 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 biblio-

graphic searching. Our aim was to provide a review that cov-

ered 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 in-

dividual studies, we did not undertake any formal grading of

the quality of evidence given the large diversity of study types.

Similarly, we did not attempt any meta-analysis given the vari-

ation 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

How common is acne?

A degree of acne affects nearly all people between the ages of

15 and 17 years11–13 and in 15–20% of young people, acne is

moderate to severe.11,14,15 Prevalence rates of acne by age16

and 1996 census data estimated that 40–50 million U.S. indi-

viduals have acne, with an 85% prevalence rate in those aged

12–24 years.17 A study by Lucky et al.18 found that the sever-

ity of acne in boys correlated with pubertal maturation and

that 50% of 10- and 11-year-old boys had more than 10 com-

edones. Another study by the same team showed that 78% of

girls between aged 8 and 12 years had acne.19 Of note, the

severity of acne increased with advancing maturity and prepu-

bertal girls with severe acne had notably higher dehydroepi-

androsterone sulphate levels.18,19 Acne consistently represents

the top three most prevalent skin conditions in the general

population as found in large studies in the U.K., France and

the U.S.A.20–22

How long does acne last?

Acne begins in the early teens with the onset of facial sebum

production and facial comedones followed by inflammatory le-

sions.14,23 Acne can occur in prepubertal children but this is

usually noninflammatory in nature as children have not yet

begun production of sebum, which provides the correct envi-

ronment to host P. acnes.24 Around 20% of neonates have an

acneiform eruption but this usually resolves by 3 months.25

One Danish study has shown that the average age at onset of

puberty in boys has dropped from 11Æ92 to 11Æ66 years over a

15-year period.26 Friedlander et al.24 postulated that this youn-

ger age of puberty was the reason for the observation that

younger patients between the ages of 8 and 11 were present-

ing with acne in their clinics. Acne is a chronic disease and

can persist, in some cases, into adulthood,27–29 for unclear rea-

sons.30 A German population study found 64% of those aged

20–29 years and 43% of those between 30 and 39 years had

visible acne31 and another study of 2000 adults found that 3%

of men and 5% of women still had a degree of acne between

the ages of 40 and 49.32 Sequential prevalence studies showing

that acne decreases with age are not as strong as cohort studies

that document natural history of acne over time in the same

individuals. Self-reported acne studies are unreliable.33 We

found few high-quality cohort studies of acne, which may be

because studies of this nature are often difficult to conduct par-

ticularly due to the widespread availability of acne therapy.

Fig 1. Moderate inflammatory acne accompanied by scarring.


BJD � 2012 British Association of Dermatologists 2013 168, pp474–485

Epidemiology of acne vulgaris, K. Bhate and H.C. Williams 475

Additionally, the definition of acne and its severity has varied

so much over time that it is difficult to compare and collate

the results of different studies. A validated and universal out-

come measure needs to be employed for future studies.10 Pre-

dictors of acne severity include family members with acne and

the early onset of comedonal acne.14,34 Longitudinal studies in

the natural history of acne are required, in particular with a

view to identifying risk factors for severe disease. It is

unknown whether or not prepubertal treatment can alter P.

acnes colonization and therefore subsequent inflammatory acne.

Acne vulgaris and its association with self-consciousness,

anxiety in social interaction, dissatisfaction with appearance

and overall impaired quality of life is well reported.11,35,36 A

recent review of studies by Dunn et al.37 concluded that acne

can negatively affect quality of life, self-esteem and mood,

and increase the risk of anxiety, depression and suicidal idea-

tion. Female subjects score worse than males in the Dermatol-

ogy Life Quality Index and acne quality of life self-assessment

score, and impact upon quality of life is associated with

longer acne duration.38–40 Depression and anxiety are often

seen more in female subjects.40–43 The media’s portrayal of

flawless skin as an ideal is in part a culprit of psychological

morbidity in females.44 Halvorsen et al.45 in a well-conducted

questionnaire-based cross-sectional survey found suicidal idea-

tion and substantial acne to have a threefold increase com-

pared with mild acne in male subjects. Magin et al.46 on the

other hand, in a prospective cohort study in 244 subjects,

found no correlation between acne and acne severity and psy-

chological or psychiatric morbidity, although the study would

have benefited from longer follow-up. An association with

low attachment to friends and not thriving at school has also

been noted.45 Quality of life does not always correlate with

acne severity,47,48 although some surveys have noted a correl-

ation.49,50 The presence of acne lowers the perception of over-

all health,51 and teasing and bullying is also a significant cause

of morbidity.52

Socioeconomic impact

A large cohort study in Canada found that those of low socio-

economic background were referred less to dermatologists

than those of a higher socioeconomic background and, add-

itionally, 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 pro-

ductivity.57 The presence of acne has been reported to have a

negative effect upon work ⁄school performance.58 Unemploy-

ment 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-

sidered in this study.56 Anger can also be associated with

skin-related quality of life59 as well as emotional and behavio-

ural difficulties.60 Such psychosocial effects must be consid-

ered by the healthcare professional treating a patient with

acne. Although there is no definitive study on the socioeco-

nomics of acne, it is likely, given data in the literature so far,

that acne does have a significant impact upon the socioeco-

nomic potential of populations.

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 rela-

tives15 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.62–66

More recently, a prospective twin study comparing monozy-

gotic and dizygotic twins found that acne severity was geneti-

cally determined, although the low power of the study could

not rule out the influence of additional environmental fac-

tors.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 7Æ4% (163 ⁄2200) of caucasian

patients and 4Æ6% (101 ⁄2200) of black patients had acne vul-

garis. Hazen69 in 1914 found a similar frequency of acne in

2000 outpatient visits of black patients when compared with

2000 caucasian patients (8Æ4% and 9%, respectively). Such

clinic-based studies are not a good method of making infer-

ences about population characteristics as the estimates could

reflect selection bias in those attending or differences in diag-

nostic 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 dis-

crepancy. 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 condi-

tions 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 (27Æ97%) than in Mestizos (43Æ08%) or

whites (44Æ47%). Again, there is an element of selection bias



476 Epidemiology of acne vulgaris, K. Bhate and H.C. Williams

Tab

le1

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in this study as the recruited schools were selected based on

large size and, in addition, there was only one single assessor.

Recently, a population-based, self-reported, cross-sectional

survey of 2895 people found the prevalence of acne to be

greater in African-Americans and Hispanics than in caucasians,

Asians and continental Indians.74 Limitation of recruitment to

female subjects only and to four cities makes interpretation of

these results difficult. Regardless, acne is seen as the most

common dermatological diagnosis in both black and white

subjects,75,76 and the current consensus with regard to man-

agement is that there is no difference between them.77

Pathophysiology in different ethnic groups

It is unclear whether, if there are any ethnic group differ-

ences, they can be explained by differences in pathophysi-

ology. A small case series of 60 women found a greater

density of P. acnes in black-skinned individuals.78 Studies into

sebaceous gland size and activity between black and white

subjects have been too small to be conclusive and several stud-

ies have been contradictory in terms of the conclusions drawn

from their results.79–81 Sebum production increases during

puberty and the onset of puberty is earlier in black individu-

als.18,82 Most studies to date have focused on caucasian and

black skin types and there are no such studies to our knowl-

edge in Asian or Hispanic patients for comparison.83

Special problems associated with specific ethnic groups

Postinflammatory hyperpigmentation or hyperpigmented ma-

cules are a common finding in darker skin types, which may be

due to the presence of polymorphonuclear cell infiltrates even

in noninflammatory lesions, for example, comedones.84,85

Keloid scarring is seen less frequently than hyperpigmentation

but is nonetheless a serious consequence of acne in darker

skin.77 The incidence of nodulocystic acne may be lower in

African-Americans compared with caucasians and Hispanics.77

There are specific subtypes of acne that have been described

in the literature, for example, pomade acne which is seen in

African-Americans. Pomade acne occurs at the hairline second-

ary to the use of pomade (containing high-melting hydrocar-

bons) and other hair products and consists of comedones and

small papules. Similarly, steroid acne can be caused by some

skin-lightening agents containing potent topical corticosteroids

used to lighten the skin or improve hyperpigmentation.77,83,86

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 carbohy-

drate 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

sample size limits our interpretation of results.89 Nonetheless,

these findings, along with another study suggesting that high

chocolate intake does not worsen acne,90 resulted in quashing

the notion that diet was involved in acne pathogenesis and

was consequently removed from major textbooks of that time.

A concise systematic review by Magin et al.91 in 2005 of

seven studies, including one randomized controlled trial, con-

cluded that there was no clear, positive evidence that any die-

tary components increase acne risk.

The roles of iodine, vitamin A, antioxidants, omega-3 fatty

acids and fibre are not clear. Of note, however, there is some

evidence of benefit with high doses of oral zinc from double-

blind, randomized controlled trials.92,93

Care must be taken to separate those studies which evaluate

foods as a possible cause of acne occurrence as opposed to

foods which could influence severity or disease flares, as they

may not necessarily be the same. It is also important not to

discard dietary hypotheses in acne on the basis of absent or

poor evidence. Three dietary factors, chocolate, a high-GI diet

and dairy products are worthy of further discussion.

Glycaemic index

The GI quantifies the effect of ingested carbohydrates on blood

glucose levels and is calculated by a 2-h blood glucose

response curve after a 50-g carbohydrate load in 10 subjects.94

Glycaemic load is a function of the GI and portion size relating

to carbohydrates.95 The absence of acne in native non-West-

ernized people in Papua New Guinea and Paraguay have led to

the proposal that high glycaemic loads in the Western diet

could have a role in acne.96 Conversely, a questionnaire and

biochemical study found no significant differences in serum

glucose, insulin, leptin, GI or glycaemic load between patients

with acne and controls.97 In a single-blind, randomized con-

trolled trial of 43 men in which acne lesion counts and severity

were assessed monthly over a 12-week period, total lesion

counts decreased more in those on a low-glycaemic-load diet

compared with a control group who had consumed carbo-

hydrate-dense foods. Associated factors such as the weight loss

of participants and the fats and protein consumed needed fur-

ther delineation to establish what factors might have caused

the decreased lesion count, or if it was a combination of vari-

ous factors.98 As sebum is stimulated by androgens, a possible

mechanism for an association between a high-GI diet and acne

is that the hyperinsulinaemic state leads to increased androgen

along with insulin-like growth factor (IGF)-1 and altered reti-

noid signalling.95,99,100 This is an area worthy of further larger

trials with blinded outcome assessment.

Dairy

Robinson101 first described a possible role of dairy produce in

worsening acne after he studied the food diaries of 1925

patients. In 2005 Adebamowo et al.102, using a validated food

frequency questionnaire of over 47 000 women, found a

positive association between a history of acne and the intake




of skimmed milk. This study was, however, flawed because of

a high risk of recall bias and because confounding factors

were not fully taken into account. The same group then

undertook a 3-year prospective study of over 6000 girls aged

between 9 and 15 years. This study found a positive associa-

tion between the prevalence of acne and the consumption of

full-fat, skimmed and low-fat milk and no association with

nonmilk dairy foods, chocolate, pizza and French fries.103 It is

difficult to ascertain if milk was associated with the occurrence

of acne or whether it was associated with increased acne

severity. A similar study in boys found only a weak association

with skimmed milk and no association with milks of a higher

fat content.104 Again, the exact onset of acne was unknown.

All of the studies by Adebamowo et al. were limited because

acne occurrence was based on questionnaires rather than

blinded objective measurements. Additionally, the GI (a mea-

sure of carbohydrate on blood glucose over time) of skimmed

or nonfat milk is 4 and that of full-fat milk is 3,105 i.e. it may

be that the association could be explained by glycaemic load

rather than fat or dairy content per se. Another possibility is

that hormones such as the 5-a-reduced steroids, a-lactalbu-

min, testosterone precursors and IGF-1 (which stimulate the

synthesis of androgens) may still be present after the milk is

processed and the fat removed thereby going on to contribute

to acne pathogenesis.106–109 IGF-1 has been positively corre-

lated with acne.97 The evidence suggesting an association

between dairy food intake and acne is currently weak and

needs to be tested in an experimental fashion.

Chocolate

There is a well-recognized belief that chocolate causes or exac-

erbates 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: meth-

ods 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 con-

sumption of chocolate made up of 100% cocoa.113 The ques-

tion 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

Table 2 Interventional studies on chocolate and its effect upon acne

Study Design ParticipantsSamplesize Main findings Limitations

Grant and

Anderson112Uncontrolled

provocationstudy

University

students. Mildto moderate

acne

8 4 of 8 developed 5 new acne

lesions. Authors claimed notsignificant but no statistics

shown

Small sample size. Uncontrolled.

Incomplete reporting ofmethods. Possibly too short

a follow-up timeAnderson89 Uncontrolled

provocationstudy

University

students withacne who

claimed thatcertain food

exacerbatedtheir acne

Unknown One-third developed new

lesions having been givensix 39-g chocolate bars per

day for 1 week; milk,peanuts and coca cola

were also being tested

Uncontrolled. No quantitative

data, no statistics. Length offollow-up not specified.

Follow-up duration may beinadequate

Fulton et al.90 Single blind,placebo-

controlledcrossover,

randomized

Male prisoners 65 No difference in acneseverity between the two

groups

Blinding and randomizationmethods not completely

described, no intention-to-treatanalysis, just one observation in

4 weeks, the test period may

have been too long – couldtolerance have developed? The

high fat content of the placebobar may be acnegenic

Berman et al.113 Interventional,uncontrolled.

100% chocolateconsumed

Men 10 Significant increase in thenumber of acne lesions

on days 4 and 7

Small sample size. Uncontrolled,no placebo group




convincing evidence that natural sunlight improves acne.91

The manipulation of the electromagnetic spectrum into thera-

peutic benefit, however, has flooded the literature. A Cochrane

systematic review of clinical trials of light therapy published

up to 2008 found evidence for some benefit of light therapy,

in the short term at least, and therapy with blue, blue ⁄red or

infrared is of more benefit than yellow, red or green light.

Sample sizes were often small and of variable quality.114 The

increasing use of photodynamic therapy is also reported in tri-

als, again of variable quality, and while the short-term effects

are good they are limited by possible adverse effects.115 There

is limited evidence of natural sunlight and its effect upon acne

and this may be a result of such studies inherently being diffi-

cult to conduct. The use of light-based therapies may signify

evidence of sunlight being beneficial to acne sufferers, but the

risk of the development of skin cancers must be taken into

account and therefore care should be taken in advising thera-

peutic sun exposure.116

Hygiene

There is a common perception that poor levels of hygiene lead

to the development or exacerbation of acne vulgaris.117,118 A

comprehensive systematic review of 11 studies in 2005 con-

cluded that there is insufficient evidence that acne is caused

by, cured or exacerbated by washing,91 and there have been

no studies to our knowledge comparing no washing with

washing in patients with acne. Earlier observations of a possi-

ble comedogenic effect of soaps on rabbit ear were not repli-

cated in humans.119 An unblinded, randomized controlled

trial of 120 patients with acne reported less inflammatory

lesions in those using acidic soaps than those using alkaline

soaps.120 There is some evidence to suggest that medicated

washes may help acne, but the evidence is weak: one, uncon-

trolled study of 10 patients and another crossover trial of 41

patients which did not report methods of randomization or

assessment.121,122 More recently, a single-blind, randomized

controlled trial comparing washing the face with a mild

unmedicated cleanser once a day, twice a day and four times

a day found there was a statistically significant improvement

in lesion count in the twice-daily group with no worsening in

the four times-daily group.123 Some have suggested that sweat

can trigger or exacerbate acne;41 however, a single-blind, ran-

domized pilot study found no association between exercise-

induced sweat and truncal acne.124 The evidence does not

provide clear advice for or against washing as a means of

helping acne, and there is certainly no robust evidence that

acne is caused or propelled by a lack of hygiene.

Smoking

Whether or not acne is caused by, exacerbated, improved,

cured, or is not associated with smoking remains controver-

sial.31,125–130 An earlier case series suggested an inverse rela-

tionship between acne and smoking, suggesting an anti-

inflammatory effect of a component found in cigarettes.125

Later, in 2001, a larger cross-sectional analysis of 896 young

people found a statistically significant correlation between acne

prevalence and the number of cigarettes smoked per day and

a dose-dependent relationship between consumption and

severity (not affected by age, sex or social class).31 A large-

scale, questionnaire study of 27 083 military men between

1983 and 2003 found the prevalence of acne to be lower in

active smokers, with a dose-dependent inverse relationship

between severe acne prevalence and cigarette consumption

from 21 cigarettes per day and higher.131 Although it is possi-

ble that smoking could ameliorate acne, further experimental

research in this area is unethical due to the harmful effects of

smoking. Further observational research is likely to perpetuate

previous problems in reporting bias and confounding. Clini-

cians are recommended to advise against smoking despite

some evidence suggesting it is beneficial with regard to acne.

Obesity

Relatively few studies have evaluated the possible relationship

between obesity and acne vulgaris. One study of 3000 patients

between the ages of 6 and 11 years found the mean body mass

index of patients with acne to be slightly higher (19Æ5) than in

individuals without acne (18Æ2), although the clinical signifi-

cance of such a small but statistically significant difference is

questionable.132 We have already commented on a randomized

controlled trial of a high-GI diet vs. a low-GI diet, which

found that in the participants on a low-GI diet the acne

improved. A confounding factor, however, was the associated

weight loss, which needs to be studied further. Acne and obes-

ity are often seen together in polycystic ovary syndrome

(PCOS), and studies have shown less acne in the obese patients

with PCOS than in nonobese patients with PCOS.133,134

Stress and picking

Stress is perceived to be a major trigger factor in exacerbating

acne vulgaris and this has been supported by early retrospect-

ive studies.28,135,136 An interventional study in biofeedback

training, relaxation training and stress reduction techniques

found that patients with acne had an improvement in severity

compared with their controls, and when relaxation techniques

were stopped, open and closed comedones recurred.137 A

cross-sectional study of sound design by Halvorsen et al.138

found an increase in mental distress with the severity of acne,

and stressful events such as university examinations have been

correlated with increased acne severity in a prospective study

of 22 patients, despite adjusting for confounding factors such

as lack of sleep and changes in diet.139 A recent Korean

questionnaire study found that 82% of patients believed that

stressful circumstances exacerbate acne.140 Other predomi-

nantly questionnaire-based studies have similar find-

ings.15,34,41,141,142 Another study also finding acne severity to

be greater in stressful examination situations using summer

holidays as a control found that there were no differences in

sebum production during stress.143 Stress induces the local




expression of neuropeptides which may pose as a pathogenic

step in acne exacerbated or caused by stress.144 The associa-

tion between mental health problems as the result of acne

have been discussed elsewhere. A point to note is that there

have been relatively few studies examining stress as a possible

cause of acne or acne exacerbation; more studies have focused

on stress and mental health problems occurring as a result of

acne.

A very small, observational study showed that picking at

acne lesions worsened the inflammation and pustules.145 A

further study with the same group of 56 patients with acne

found that picking was more related to perfectionistic and

compulsive personality traits than acne severity.146 It is likely

that picking will ultimately affect the healing process and

increase the likelihood of scarring.

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 colo-

nizer of the anaerobic lipid-rich environment, rather than a

primary pathogen.149–151 A large, randomized controlled trial

comparing five antimicrobial regimens noted that clinical effi-

cacy of oral antibiotics was less in those with resistant strains,

suggesting that antibiotics may work through a direct antimi-

crobial as well as anti-inflammatory effect. This is a concept

that the majority of experimental studies have supported,

although not all.152–155 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 mecha-

nisms in which P. acnes is directly involved in acne pathogene-

sis, 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 proin-

flammatory cytokines; however, the exact mechanism has not

been confirmed. Pathway targets have been used for experi-

ments 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 con-

cluded that P. acnes was unlikely to have an active role in the

development of inflammatory ⁄noninflammatory acne le-

sions.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 comedo-

nes and that their pilosebaceous units are under the control of

testosterone, it is intriguing to wonder why humans are

unique in their propensity to develop acne – perhaps P. acnes

plays more of a role than an innocent bystander after all.

Conclusions

Despite many attempts at investigating the epidemiology of

acne, few studies have provided any clear answers. Observa-

tional studies, while useful at generating hypotheses, have

been generally limited by traditional drawbacks such as infor-

mation bias, confounding, reverse causation and the lack of

suitable controls. Future observational studies need to distin-

guish between those factors that may be associated with the

first appearance of acne and those with an effect upon sever-

ity, 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. Addition-

ally, 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.

What’s already known about this topic?

• Acne is a common disease affecting all to a degree,

manifesting in adolescence with significant psychosocial

and socioeconomic consequences.

What does this study add?

• This review elucidates the risk factors for the develop-

ment of and severity of acne vulgaris leading to

improved understanding.

• We highlight the need for universal outcome measures

and important areas such as the natural history of acne

and relationship between foodstuffs and acne where

more high-quality studies would be valuable.

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