Acne Vulgaris: Pathogenesis, Treatment, and Needs Assessment
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A c n e Vu l g a r i s :
Pathogenesis,
Trea tment, and
N e e d s As s e s s m e n t
Siri Knutsen-Larson, MDa,1, Annelise L. Dawson, BAa,1,
Cory A. Dunnick, MDa,*,
Robert P. Dellavalle, MD, PhD, MSPHb
KEYWORDS
Acne vulgaris Epidemiology Treatment
Acne vulgaris is a common skin condition with the absence of a universally accepted diagnostic
substantial cutaneous and psychologic disease or grading schema. Additionally, estimates
burden. Studies suggest that the emotional impact continue to change as the prevalence of acne
of acne is comparable to that experienced by decreases secondary to improved treatment
patients with systemic diseases, like diabetes modalities.9 Acne is most common in adolescents,
and epilepsy.1–3 In conjunction with the consider- affecting approximately 85% of teenagers.9,10
able personal burden experienced by patients Acne prevalence after adolescence decreases
with acne, acne vulgaris also accounts for with increasing age, but disease burden in younger
substantial societal and health care burden. Amer- adults is still quite high.8 A common misconcep-
icans use more than 5 million physician visits for tion by the medical and lay community is that
acne each year, leading to annual direct costs in acne is a self-limited teenage disease and, thus,
excess of $2 billion.4,5 Acne is the most common does not warrant attention as a chronic disease.
diagnosis made by dermatologists and is also Nevertheless, the chronicity of many cases of
commonly made by nondermatologist physi- acne as well as the well-documented psychologic
cians.6,7 The pathogenesis and existing treatment effects of chronic acne contributes to the burden
strategies for acne are complex.8 This article of the disease.2,3,11
discusses the epidemiology, pathogenesis, and The average age of onset of acne is 11 years in
treatment of acne vulgaris. The burden of disease girls and 12 years in boys.12,13 Acne is increasing
in the United States and future directions in the in children of younger ages, with the appearance
management of acne is also addressed. of acne in patients as young as 8 or 9 years of
age. This trend toward earlier development of
acne is thought to be related to the decreasing
EPIDEMIOLOGY
age-of-onset of puberty that has been observed
Acne is a highly common skin condition. Still, esti- in the United States.14 Acne is more common in
mates of acne prevalence vary substantially given males in adolescence and early adulthood, which
a
Department of Dermatology, University of Colorado Denver, PO Box 6511, Mail Stop 8127, Aurora, CO 80045,
USA
b
Dermatology Service, Denver Department of Veterans Affairs Medical Center, University of Colorado School
derm.theclinics.com
of Medicine, Colorado School of Public Health, 1055 Clermont Street, Mail Code #165, Denver, CO 80220, USA
1
Both authors contributed equally to this article.
* Corresponding author. Department of Dermatology, University of Colorado Denver School of Medicine,
Aurora Court F703, PO Box 6510, Aurora, CO 80045.
E-mail address: cory.dunnick@ucdenver.edu
Dermatol Clin 30 (2012) 99–106
doi:10.1016/j.det.2011.09.001
0733-8635/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.100 Knutsen-Larson et al
is a trend that reverses with increasing age.12,13 It hyperplasia, and various endocrine tumors, result
is well known that adult acne is more common in in a higher circulating level of androgens and
women. Adult acne typically represents chronic are associated with the development of acne
acne persisting from adolescence, not new-onset vulgaris.27
disease.15,16 The corporal distribution of acne depends on pi-
Other factors impacting acne prevalence and losebaceous gland density and morphology and,
severity include ethnicity and genetic propensity. thus, is common in regions where these structures
Acne age of onset and disease character vary are largest and most abundant: the face, chest,
among patients of different ethnicities. Scarring neck, and back. Noninflammatory acne is charac-
and pigmentary changes are common in skin of terized by the formation of open or closed
color. Propensity to scar and to develop hyperpig- comedones. Open comedones, or blackheads,
mentation is highest among Hispanic and African demonstrate darkly colored hyperkeratotic plugs
American patients, respectively.12,17 These long- within the follicular opening. This dark coloration
term disease consequences are challenging to is related to the oxidation of melanin and not dirt,
treat and contribute to the disease burden. In as is a common public misconception. Closed
addition, genetic factors impact the propensity comedones, or whiteheads, are white to flesh
to develop acne. Adolescent and adult acne is toned in color and seem not to have a central
more common in children of parents with a history open pore.25
of acne.12,18,19 Changes in the skin’s natural flora accompany
Several modifiable factors alter acne risk. Ciga- this androgen-related increase in sebum produc-
rette smoking, for example, raises acne risk with tion. Propionibacterium acnes, a normal compo-
disease severity worsening in a dose-dependent nent of the cutaneous flora, inhabits the
fashion with increasing number of cigarettes pilosebaceous unit using lipid-rich sebum as
smoked daily.13 Although evidence regarding the a nutrient source. P acnes, therefore, flourishes
impact of dietary factors on acne is equivocal, in the presence of increased sebum production,
studies suggest that dairy intake increases acne leading to inflammation via complement activa-
risk.20–22 Finally, traditional opinion in dermatology tion and the release of metabolic byproducts,
holds that acne tends to improve during summer proteases, and neutrophil-attracting chemotactic
months when sun exposure is greater. 23 This factors.25,28 Inflammatory acne vulgaris lesions,
finding is supported by an observed seasonal such as papules, pustules, nodules, or cysts,
decrease in physician visits for acne during develop when comedones rupture and contents
summer months.24 Nevertheless, no studies exist of the pilosebaceous unit spill into the surrounding
to support this association and use of UV light to dermis.25,29 In severe cases, adjacent cysts may
treat acne has been rejected.23 Undoubtedly, coalesce to form channels or draining sinuses.
acne is a complex disease process influenced by Inflammatory acne may produce cutaneous scar-
both genetic and environmental factors. ring or hyperpigmentation that persists long after
acne resolution.25
PATHOGENESIS
PREVENTION
The pathogenesis of acne is a result of multifac-
eted processes within the pilosebaceous unit re- External factors play an important role in the devel-
sulting in bacterial overgrowth and inflammation. opment of acne lesions. Cigarette smoking and
This condition typically develops at the time of dietary factors increase acne risk and disease
the pubertal transition when changes in the body’s severity. In addition, certain skin and hair products
hormonal milieu alter pilosebaceous gland func- and use of occlusive clothing articles contribute to
tion. Initially, follicular epithelial cells differentiate acne development. The removal of any of these
abnormally and form tighter intracellular adhesions factors may lead to an improvement in disease
and, therefore, are shed less readily. This process severity.
leads to the development of hyperkeratotic plugs, The link between smoking and acne is well es-
or microcomedones, which enlarge progressively tablished.13 Even though smoking avoidance and
to form noninflammatory, closed or open come- cessation should be encouraged in all patients,
dones. 25 Circulating and cutaneously derived this preventive message is especially important
androgens, often named the primary inciting factor for patients suffering from acne. Practitioners
in the development of acne, induce sebum should emphasize not only that smoking increases
production, further contributing to the develop- acne risk but also that a dose-dependent relation-
ment of comedones.26 Conditions, such as poly- ship exists between daily cigarette use and acne
cystic ovarian syndrome, congenital adrenal disease severity.Acne Needs Assessment 101
The controversial relationship between diet and A primary initial treatment approach is proper
acne has been studied for many years. There is no skin care. This care includes eliminating the afore-
reputable evidence to support a link between acne mentioned extrinsic factors as well as encouraging
and chocolate. Recently, however, studies have proper skin hygiene and adherence to prescribed
suggested an association between milk and acne treatment regimens. Although it was previ-
acne.20–22 This finding is based on increased ously thought that excessive skin cleansing
levels of insulinlike growth factor 1 in milk causing contributes to the formation of acne, several small
an increase in circulating androgens. Associations studies indicate that facial cleansing, even when
of omega-3 fatty acids, antioxidants, zinc, vitamin performed up to 4 times daily, is not harmful and
A, and iodine with acne have also been proposed. may, in fact, diminish acne severity.38–40 Patient
However, all of these areas require further education in proper hygiene includes counseling
research.30 Dietary modification alone is not regarding appropriate skin cleanser and moistur-
adequate for acne prevention regardless of the izer selection.41
association between diet and acne. Individuals If skin care alone does not lead to the resolution
with acne wishing to make dietary changes should of cutaneous lesions, topical and systemic antimi-
focus on the avoidance of dairy products as crobials may be used. Topical antibiotics may be
perhaps the most evidence-based intervention. used to treat mild to moderate acne. Systemic
Facial and hair products, especially cosmetics antibiotics are indicated when acne is moderate
and hair products containing oils, may lead to an to severe or if disease manifestations are
exacerbation of acne lesions.17,31 In addition, producing marked psychosocial stress for
repeated scrubbing with soaps, detergents, and patients.28 The purpose of this treatment modality
other agents can cause trauma to underlying is to decrease the presence of P acnes on the skin
comedones, thereby increasing inflammation. surface and within the pilosebaceous unit.42 Anti-
Thus, individuals with acne should select oil-free biotics confer more than antimicrobial properties.
or noncomedogenic products and refrain from They also produce antiinflammatory effects, inhibit
aggressively rubbing the face.32 Other factors neutrophil chemotaxis, and alter compliment path-
also contribute to pore occlusion, including tight ways, all of which aid in the treatment of acne.28
clothing and head gear. Hence, these articles Various classes of antibiotics, such as sulfon-
should be avoided when possible. amides, macrolides, tetracyclines, and dapsone,
may be used to treat acne.28,42
TREATMENT Widespread and long-term use of antibiotics
has led to the development of P acnes resistance
In the United States, there is an overabundance and has also been associated with Staphylo-
of treatment recommendations for patients with coccus resistance.28,43,44 Thus, when treating
acne. Unfortunately, few of these recommenda- with antimicrobials, the prescribing clinician must
tions are evidenced based and comparative consider not only local patterns of resistance but
studies are limited.33 In fact, in 2009, the Institute also patient adherence to a regimen that will not
of Medicine listed acne as a priority for comparative promote selection for resistant bacterial strains.
effectiveness research evaluating treatment regi- It is also important to avoid protracted antibiotic
mens.34 Recently published treatment algorithms courses. Monotherapy with antimicrobials should
include A Global Alliance to Improve Outcomes be avoided, especially when using macrolides
in Acne, those endorsed by the American that are most often associated with the develop-
Academy of Dermatology, and recommendations ment of resistance.28,44 Instead, successful treat-
from a European expert group on oral antibiotics ment is often seen when pairing antimicrobials
to treat acne.32,35,36 These recommendations are with benzoyl peroxide, hormonal therapies, and
based on expert opinion given the limited evidence retinoid preparations.28,42
available. All of the guidelines recommend similar In women with mild to moderate acne,
approaches focusing on acne severity and degree combined oral contraceptives (COCs) can be
of inflammation. In addition, acne treatment recom- used. A recent Cochrane review concluded that
mendations may be based on skin type, clinical this method of treatment reduces acne severity
classification of acne, and preexisting acne when compared with placebo.45 Even though
scaring.37 Treatment options include proper skin androgen levels are often normal in women with
care, topical and oral antimicrobials, topical and acne vulgaris, hormonal therapies combating
systemic retinoids, benzoyl peroxide, and oral androgens seem to benefit these patients.46
contraceptives for female patients. These treat- Progestins tend to be proandrogenic but most
ments are often used in combination to achieve COCs are estrogen dominant. Estrogen containing
disease resolution. oral contraceptives increase circulating levels of102 Knutsen-Larson et al
steroid hormone binding globulin which results in common atrophic scars and hypertrophic scars.
lower circulating levels of testosterone. Different Treatments for acne scarring include, but are not
COCs contain varying levels of progestins and limited to, topical treatments, chemical peels,
the implications of this require further research.45 dermabrasion, laser, and dermal grafting. Unfortu-
In women with mild to moderate acne who do nately, there are no well-accepted guidelines to
not desire childbearing, COCs are a good treat- optimize acne scar treatment. Additional research
ment recommendation. Oral contraceptives are is required to determine cost-effectiveness and
often paired with other acne therapies.32 establish the duration of treatment effects.52
Topical retinoids represent the most commonly
prescribed treatment option because they are BURDEN OF TREATMENT
effective in both the treatment and prevention of
acne.47 The mechanism of action of retinoids The annual cost of acne treatment is quite high
involves preventing the primary acne lesion, which given the prevalence and chronicity of the
decreases inflammation.48 This drug class is an disease. Acne represents the most common
excellent choice for both initial and maintenance dermatologic diagnosis in the United States.6,7
therapy and assists many patients in achieving A study based on data from 2004 estimates that
adequate disease control. Depending on the the annual direct cost of acne management is
case, topical retinoids can be paired with more than $2.5 billion. Acne ranks second only
benzoyl peroxide, antimicrobials, or with oral to skin ulcers and wounds in annual cost burden
contraceptives. for dermatologic illness.4
Finally, oral isotretinoin is an option for severe, In addition to the high cost burden, the treat-
refractory acne. The mechanism of action includes ment of acne produces heavy physician demands.
decreasing sebaceous gland activity with a resul- Acne accounts for more than 5 million physician
tant decrease in sebum secretion. This action visits annually, or approximately 8% of all derma-
effectively diminishes overgrowth of P acnes, tologic health care visits.5,7,53 Two-thirds of physi-
which is a key pathogenic factor. The drug also cian visits for acne are made by women,
inhibits keratinocyte hyperplasia and instead suggesting that women are more likely than men
promotes normal differentiation.49 Isotretinoin to seek medical care for acne.53,54 Contrary to
must be prescribed carefully because it carries the perception of acne as a disease of adolescents
several black box warnings, including teratoge- only, individuals aged older than 18 years account
nicity, possible change in mood status, and hyper- for more than 60% of acne-related visits. Never-
triglyceridemia, among others.49,50 This drug is the theless, the health care burden of adolescent
only acne treatment option that permanently acne is substantial, with patients aged 12 to 17
changes the course of the disorder. However, years composing nearly 40% of the visits.
because of the considerable side effects, it should Although recent studies have demonstrated an
only be used in those with refractory nodular acne. increase in acne prevalence for children aged
Given the increasing trend toward treatment younger than 12 years, these patients account
with several agents simultaneously, providers for the minority of health care visits or less than
have come to rely on the use of combination 2% of all physician visits for acne.54
agents in the treatment of acne. These agents
include pairings of topical antibiotics with benzoyl AVAILABLE SERVICES
peroxide, topical antibiotics with retinoids, and
others. Use of combined agents has been demon- Acne vulgaris is managed in the outpatient setting
strated to improve patient adherence to by both specialist and generalist physicians.
prescribed regimens.51 Given that poor adherence Dermatologists provide approximately two-thirds
to complex medication regimens limits treatment of all acne care in the United States, followed by
efficacy and contributes to the chronicity and pediatricians (16%), general/family practitioners
burden of acne, providers should aim to simplify (12%), internists (5%), and obstetricians/gynecol-
treatment regimens and use combined agents ogists (1%).55 Long wait times and poor geo-
when feasible. graphic distribution of the dermatologic workforce
are 2 factors thought to promote the use of non-
ACNE SCARRING dermatologist care in acne treatment.56,57 Further-
more, several characteristics, including being
Despite the many treatment options, acne scars younger than 18 years of age, Hispanic ethnicity,
still develop in some patients. They result from receipt of care in the West or Midwest, and the
skin damage during the healing process of acne. use of public medical insurance, are predictive of
Acne scars are divided into 2 groups: more nondermatologist acne care.55Acne Needs Assessment 103 Use of nondermatologist care in acne treatment dermatologists in their geographic region. Acne- is relevant because it may not be equivalent to the Net (http://skincarephysicians.com/acnenet/ care provided by dermatologists. Studies report index.html) provides similar patient material on- differences in prescribing patterns and varying line. Social networking and other online media regimen complexity between dermatologists and sources host abundant content describing acne general practitioners. In particular, generalists are management. Although much of this online less likely to prescribe topical retinoids and are content is unregulated and should be interpreted more likely to prescribe antibiotic monotherapy, carefully, numerous reliable health information which are trends not in line with the present sources exist. Physicians should be aware of recommendations.47,58 the many accurate online resources to which Overall, generalists receive limited training in the they can direct patients as well as the unregulated treatment of dermatologic disease. US medical content their patients may be accessing. schools provide on average only 21 hours of dermatology training before graduation, and FUTURE DIRECTIONS dermatologic training in pediatric and internal medicine residencies is limited.59–61 Dermatolo- Going forward, several priorities should guide gists diagnose acne many times more frequently acne research and management efforts. First, it then do their generalist counterparts and this is imperative that comparative effectiveness quantity of experience also contributes to the research is emphasized and evidence-based expertise of dermatologists in treating acne.7,62 treatment strategies are established for acne. Even so, the role of nondermatologist care of Not only will this enhance patient outcomes but acne should not be undervalued, given the this will also allow for better control of the costs substantial burden of acne. Medical school and and physician demands associated with acne residency training programs should place greater treatment. The establishment of optimal treatment emphasis on dermatologic education. Future regimens would be expected to diminish the chro- efforts to develop standardized, evidence-based nicity and, hence, burden of acne disease. acne treatment guidelines may assist nonderma- Furthermore, standardized recommendations tologists in providing comparable acne care. would help enable nondermatologist physicians In addition to the acne treatment by physicians, to provide appropriate care and assist in meeting there has also been a growing trend toward the the demands of acne management. Likewise, use of physician assistants (PAs) and other midle- medical school and residency training programs vel providers in the management of dermatologic must emphasize dermatology education. General- disease. In fact, dermatologists are second only ists commonly manage dermatologic illness and to ophthalmologists in their use of PAs. In 1997, their ability to effectively do so relies heavily on 1 in every 32 patients visiting a dermatology clinic adequate training. was seen by a PA, which is a proportion that is Efforts to explore alternative care resources thought to have increased markedly since that should be supported. Already, the use of PAs time. PAs work under the supervision of a physi- and other midlevel providers has been established cian; however, more than one-quarter of patients in dermatologic practice. Further analyses of the seeing a PA for dermatologic complaints are not efficacy and cost-effectiveness of midlevel directly evaluated by a physician.63 To the authors’ provider care should be pursued. Additionally, in knowledge, no exact figures are available for the recent years, the use of the teledermatology and use of PAs in the treatment of acne specifically. Internet-based dermatologic care in the treatment Nevertheless, anecdotal experience indicates of acne has been explored. The use of digital that acne is a condition commonly managed by images to monitor treatment progress has been dermatology PAs and that the use of PAs to eval- proposed and may be reliable with certain assess- uate acne may diminish the costs associated with ment measures, such as total inflammatory lesion acne management. Further analyses of the effi- count.64 Similarly, online follow-up visits for acne cacy and cost of PA management of acne are have been demonstrated to produce equivalent warranted. patient outcomes.65 The use of digital and online In addition to the care resources offered resources to treat acne may diminish cost burden through physicians and midlevel providers, many and assist in making dermatology services avail- online resources are available to patients suffering able to patients in regions with limited dermato- from acne. The American Academy of Derma- logic resources. tology (www.aad.org) offers detailed patient infor- Finally, cellular phone and Internet technology mation on acne and also hosts a searchable may be used to promote adherence to treatment database that aids patients in locating regimens through the use of patient reminders.
104 Knutsen-Larson et al
dermatologists: is decreasing the number of derma-
List of Acronyms
tologists the appropriate response? Dermatol Online
COCS Combined oral contraceptives J 1998;4(1):3.
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IGF-I Insulin like growth factor I
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