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Evidence-Based Recommendations For The Diagnosis and Treatment of Pediatric Acne
Evidence-Based Recommendations For The Diagnosis and Treatment of Pediatric Acne
Cincinnati College of Medicine and Cincinnati Children’s Hospital formed and articles identified, reviewed, and assessed for evidence
Medical Center, Cincinnati, Ohio; fDepartments of Pediatrics and grading. Each topic area was assigned to 2 expert reviewers who de-
Dermatology, Northwestern University Feinberg School of veloped and presented summaries and recommendations for critique
Medicine and Division of Dermatology, Ann & Robert H. Lurie
Children’s Hospital of Chicago; gThe Ronald O. Perelman
and editing. Furthermore, the Strength of Recommendation Taxonomy,
Department of Dermatology, New York University School of including ratings for the strength of recommendation for a body of
Medicine, New York, New York; hSection of Pediatric Dermatology, evidence, was used throughout for the consensus recommendations
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
for the evaluation and management of pediatric acne. Practical
and Departments of Pediatrics and Dermatology, Perelman
School of Medicine at the University of Pennsylvania; evidence-based treatment algorithms also were developed.
iDivision of Pediatrics and Hospital Medicine, Rady Children’s
RESULTS: Recommendations were put forth regarding the classifica-
Hospital, San Diego, California and Department of Pediatrics,
University of California, San Diego, California; jDepartment of tion, diagnosis, evaluation, and management of pediatric acne, based
Dermatology, Jefferson Medical College, Thomas Jefferson on age and pubertal status. Treatment considerations include the use
University, Philadelphia, Pennsylvania; kDepartment of of over-the-counter products, topical benzoyl peroxide, topical
Dermatology, The Pennsylvania State University College of
Medicine; and lDepartment of Pediatrics, Penn State Hershey
retinoids, topical antibiotics, oral antibiotics, hormonal therapy, and
Children’s Hospital, Hershey, Pennsylvania isotretinoin. Simplified treatment algorithms and recommendations
KEY WORDS are presented in detail for adolescent, preadolescent, infantile, and
pediatric acne, acne treatment, combination acne therapy, neonatal acne. Other considerations, including psychosocial effects
retinoids, benzoyl peroxide, bacterial resistance, isotretinoin, of acne, adherence to treatment regimens, and the role of diet and
hormonal therapy, acne guidelines, acne algorithm, neonatal
acne, infantile acne, mid-childhood acne, preadolescent acne, acne, also are discussed.
American Acne and Rosacea Society, AARS CONCLUSIONS: These expert recommendations by the American Acne
(Continued on last page)
and Rosacea Society as reviewed and endorsed by the American Acad-
emy of Pediatrics constitute the first detailed, evidence-based clinical
guidelines for the management of pediatric acne including issues of
special concern when treating pediatric patients. Pediatrics 2013;131:
S163–S186
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TABLE 2 Expert Panel Consensus: Pediatric cheeks, chin, eyelids, and forehead, but mass.12 Should workup for a hormonal
Acne Categorized by Age
the scalp, neck, and upper chest and anomaly be considered, a pediatric
Acne Type Age of Onset back may be involved.8 Its pathogene- endocrinology referral and/or bone
Neonatal Birth to #6 wk sis may involve colonization with age and serologic evaluation of follicle-
Infantile 6 wk to #1 y
Mid-childhood 1 y to ,7 y
Malassezia species, a normal com- stimulating hormone, luteinizing hormone,
Preadolescent $7 to #12 y or menarche mensal of infant skin, or may represent testosterone, and dehydroepiandros-
in girls an inflammatory reaction to a yeast terone sulfate levels are recommended.
Adolescent $12 to #19 y or after overgrowth at birth.8,10 NCP is typically No further workup is necessary for the
menarche in girls
mild and self-limited, and reassuring majority of cases in the absence of
the parents is usually the only man- hormonal abnormalities. It is also im-
adolescence. In general, acne is un- agement needed. If lesions are nu- portant to distinguish true infantile
complicated by systemic disease, but merous, 2% ketoconazole cream may acne from other similar cutaneous
in some cases it may be a cutaneous reduce fungal colonization.11 New- lesions, because there is some evidence
manifestation of underlying pathology. borns also may present with or develop that infantile acne predisposes to more
It is essential to have a broad un- transient neonatal pustular melanosis, severe adolescent acne.13 Infantile acne
derstanding of acne at different ages with pustules on the chin, neck, or may be treated with topical antimicro-
and to be aware of the differential di- trunk. Within 24 hours, these pustules bial agents; topical retinoids; noncycline
agnoses for each age group. Table 3 rupture, leaving hyperpigmented mac- antibiotics, such as erythromycin; and,
presents a differential diagnosis for ules with a rim of faint white scale.10 occasionally, isotretinoin, though all are
acne in each age group.5–7 Workup is Consensus Recommendation: without FDA indication for use in this
based on age and physical findings.6 age group.
Neonates may have true acne, al-
The physical examination should focus Consensus Recommendation:
though many self-limited papulo-
on type and distribution of acne
pustular eruptions also occur on Most infantile acne is self-limited
lesions, height, weight, growth curve,
the faces of neonates. In infants and not associated with underlying
and possible blood pressure abnor-
and younger children (,7 years endocrine pathology. However, in
malities. Signs of precocious sexual
of age) with significant acne vulga- patients with additional physical
maturation or virilization should prompt
ris, evaluation for signs of sexual signs of hormonal abnormality,
workup and/or a referral to a pediatric
precocity, virilization, and/or growth a more extensive workup and/or
endocrinologist.8
abnormalities that may indicate an referral to a pediatric endocrinol-
Consensus Recommendation: underlying systemic abnormality ogist may be appropriate. (SOR: C).
Acneiform eruptions from the neo- (endocrinologic diseases, tumors,
natal period through adolescence gonadal/ovarian pathology) and ap- Mid-Childhood Acne
may be broadly categorized by age propriate workup and/or referral to
Mid-childhood acne presents primarily
and pubertal status. a pediatric endocrinologist may be
on the face with a mixture of comedones
warranted. (SOR: C).
and inflammatory lesions.10 Children
between the ages of 1 and 7 years,
Neonatal Acne Infantile Acne however, do not normally produce
Neonatal acne is estimated to affect up Infantile acne may begin at ∼6 weeks of significant levels of adrenal or gonadal
to 20% of newborns.9 The major con- age and last for 6 to 12 months or, androgens; hence, acne in this age
troversy in this age group is whether rarely, for years. It is more common in group is rare. When it does occur, an
the lesions truly represent acne or one boys and presents with comedones as endocrine abnormality should be sus-
of a number of heterogeneous pap- well as inflammatory lesions, which pected. A workup by a pediatric endo-
ulopustular acneiform conditions typi- can include papules, pustules, or oc- crinologist is usually warranted to rule
cally without comedones, such as casionally nodular lesions. Physical out adrenal or gonadal/ovarian pa-
neonatal cephalic pustulosis (NCP) or examination should include assess- thology including the presence of
transient neonatal pustular melanosis. ment of growth including height, androgen-secreting tumors. Increased
Although rare, some neonates may weight, and growth curve; testicular bone age and accelerated growth, as
present with androgen-driven come- growth and breast development; pres- evidenced by deviation from standard-
donal and inflammatory acne.8,10 NCP ence of hirsutism or pubic hair; clito- ized age-appropriate growth curves,
pustules are usually confined to the romegaly; and increased muscle are important indicators of the effects
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more visible and can darken to form an treatment as patients may not recog- Although no single acne treatment,
open comedo (blackhead). Follicular nize the improvement or think they apart from isotretinoin, addresses all 4
colonization with P acnes leads to in- have scarring. Effective and early pathogenic factors, it is now clear that
flammation via the production of inflam- treatment is essential to prevent many of the medications traditionally
matory mediators and the formation of scarring as well as postinflammatory used to treat acne actually act by more
inflammatory papules and pustules. changes and to limit the long-term than 1 mechanism. In addition to tar-
Nodular acne is characterized by a physical and psychological impact of geting the largest number of patho-
predominance of large inflammatory acne. genic factors, the approach to pediatric
nodules or pseudocysts and is often It has been repeatedly demonstrated acne should be to use the least ag-
accompanied by scarring or the pres- that acne can have a significant adverse gressive regimen that is effective while
ence of sinus tracts when adjacent impact on quality of life, and that the avoiding regimens that encourage the
nodules coalesce. level of distress may not correlate di- development of bacterial resistance.
Acne severity may be classified clini- rectly with acne severity.18,19 In 1 study, Educating a patient (and parents) about
cally as mild, moderate, or severe based assessments using several quality of reasonable expectations of results and
on the number and type of lesions and life instruments revealed deficits for discussing management of treatment-
the amount of skin involved. Although acne patients who did not correlate related side effects can maximize
there are numerous grading systems by with clinical assessments of severity.20 both compliance and efficacy.
which to define acne severity, there is no Reported social, psychological, and Numerous medications are available to
agreed-upon standard, and interpre- emotional symptoms were as severe as treat acne. Design of an effective regi-
tation is subjective. Many grading sys- those reported by individuals with men is facilitated by an increased un-
tems are most useful for research chronic medical conditions such as derstanding of the mechanisms of
purposes. For clinical purposes, sim- chronic asthma, epilepsy, diabetes, and action, the side effect profile, and the
plicity is key. Typically, patients’ as- back pain or arthritis. Adolescents, in indications and contraindications of
sessments do not correlate well with particular, may be insecure about their key antiacne agents discussed later.
either those of physicians or published appearance and vulnerable to peer
severity scales.17 The panel noted that opinions. Because social functioning OVER-THE-COUNTER TREATMENT
severity scales frequently overemphasize and quality-of-life decrements may not OPTIONS
inflammatory lesions. For example, in correlate with disease severity, even
Nationwide television commercials and
some research settings, a patient mild acne may be more troubling to
magazine ads abound with over-the-
might be classified as having mild young patients than they are willing to
counter (OTC) products. Although largely
acne because he or she has only a few admit.21
untested in controlled clinical trials,
inflammatory lesions in the presence Consensus Recommendation: many of these products are considered
of hundreds of closed comedones. In Acne can be categorized as pre- somewhat effective, particularly for
such cases, the patient (and the phy- dominately comedonal, inflamma- patients with mild acne. Those which
sician) is more likely to consider his tory, and/or mixed. Presence or have been tested include salicylic acid-
or her acne to be severe. Determin- absence of scarring, PIH, or ery- containing topical products and many
ation of severity can be modified by thema should be assessed. Sever- benzoyl peroxide (BP) products de-
extent of involvement and scarring as ity may be broadly categorized as scribed in further detail later. Salicylic
well. mild, moderate, or severe. (SOR: A). acid has revealed some efficacy in acne
Although some acne may resolve with- trials, although when tested head-to-
out residual changes, inflammatory head with other topicals, particularly BP,
acne may result in the formation of APPROACH TO PEDIATRIC ACNE it is generally less effective.22,23 Nonpre-
significant scars. In darker skin, post- THERAPY scription, nonbenzoyl-peroxide-containing
inflammatory hyperpigmentation (PIH) The therapeutic objectives in acne are products appear to be somewhat ef-
is common. Residual erythema can oc- to treat as many age-appropriate fective for the treatment of acne, espe-
cur as well. These changes are most pathogenic factors as possible by re- cially mild acne, though there is limited
often reversible but can take many ducing sebum production, preventing published evidence supporting their
months to fully resolve. Recognizing the formation of microcomedones, efficacy in the treatment of acne.
these as secondary changes is impor- suppressing P acnes, and reducing in- Sulfur, sodium sulfacetamide, and
tant when determining the efficacy of flammation to prevent scarring. resorcinol are active ingredients in
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In addition, some topical retinoids TABLE 4 Formulations and Concentrations of Topical Retinoids
also have direct antiinflammatory Retinoid Formulationa Strength, % Pregnancy Category
activity.43,51,52 At present, 3 topical Tretinoin Cream 0.025, 0.05, 0.1 C
retinoids (tretinoin, adapalene, and Gel 0.01, 0.025
Gel (micronized) 0.05
tazarotene) are available by pre- Microsphere gel 0.04, 0.1
scription in the United States. Each is Polymerized cream 0.025
available in a variety of formulations Polymerized gel 0.025
Adapalene Cream 0.1 C
and concentrations (Table 4).53 Their
Gel 0.1, 0.3
most common adverse effects include Solution 0.1
burning, stinging, dryness, and scal- Lotion 0.1
ing.15 These effects may be reduced by Tazarotene Gel 0.05, 0.1 X
Cream 0.05, 0.1
initiating treatment with the lowest
Adapted from Imahiyerobo-Ip and Dinulos.52
strength, typically sufficient to treat a Numerous generic retinoids are available. Branded products are available under the following trade names: Atralin, Avita,
mild acne, or by recommending regular and Retin-A Micro for tretinoin; Differin for adapalene; and Tazorac for tazarotene.
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hyperpigmentation may occur in some also referred to as pseudotumor cerebri. Second-generation tetracyclines
patients treated with minocycline and A high index of suspicion is warranted (doxycycline, minocycline) are some-
appears to correlate with cumulative if headache and visual disturbances, times preferred to tetracycline be-
drug exposure over time in most sometimes accompanied by nausea cause of ease of use, fewer problems
cases reported with use of immediate- and/or vomiting, are noted to detect BIH with absorption with food and min-
release minocycline formulations av- early because persistence can lead to erals in vitamins and other supple-
ailable since 1971.81–83 Weight-based severe loss of vision, which may be ments, and less-frequent dosing.
dosing of minocycline (1 mg/kg per permanent.88 (SOR: C).
day) using the extended-release tablet In the past 20 years, P acnes has be- Patients should be educated and
formulation once daily, available since come less sensitive to oral and topi- monitored for potential adverse
mid-2006, may potentially reduce the cal antibiotics because of increasing events when utilizing oral antibiot-
risk of hyperpigmentation as both the selection pressure arising from their ics for acne. (SOR: B).
peak serum level and total drug ex- widespread usage.60,66,70,89 However,
posure are diminished as compared strategies listed in Table 6 can mini- Topical Dapsone
with immediate-release minocycline mize the potential for the de- Dapsone, a synthetic sulfone, has anti-
formulations; however, continued phar- velopment of resistance to antibiotics microbial and antiinflammatory effects;
macosurveillance is warranted to con- when used to treat acne, especially as however, its activity in the treatment
firm this preliminary observation.84 the duration of therapy is often pro-
Face, trunk, legs, oral mucosa, sclera, longed over months. Recent studies
and nail beds should be examined pe- have revealed that the use of sys-
riodically. TABLE 6 Strategies to Optimize Oral
temic antibiotics for acne treatment Antibiotic Therapy in Acne Vulgaris
Acute vestibular adverse events (ie, also may be associated with an in-
crease in resistant coagulase-negative Use in moderate or severe inflammatory acne
vertigo, dizziness) that sometimes vulgaris in combination with a topical regimen
occur in patients treated with mino- staphylococci and a possible in- that includes BP.
cycline develop early after initiation of creased risk of upper respiratory Avoid antibiotic monotherapy when using either an
tract infection; however, further oral or topical antibiotic agent for acne vulgaris.
treatment and are reversible with Discontinue (or taper) within 1 to 2 mo once new
discontinuation of therapy.85–87 Weight- studies are needed to evaluate the inflammatory acne lesions have stopped
based dosing of extended release- true clinical implications of these po- emerging.
minocycline (1 mg/kg once daily) has tential risks.60,90 Incorporate a topical retinoid into the regimen
early to augment overall therapeutic benefit and
been reported to reduce the risk for Consensus Recommendations: prepare for discontinuation of oral agent with
development of acute vestibular ad- Oral antibiotics are appropriate goal of maintaining control with topical
program; may also use BP-containing
verse events as compared with a daily for moderate-to-severe inflamma- formulation with topical retinoid for
dose up to threefold higher.61 tory acne vulgaris at any age. Tet- maintenance of control of acne.
A rare central nervous system-related racycline derivatives (tetracycline, If retreatment is needed, use the same oral
antibiotic that was previously effective in the
side effect associated with use of tet- doxycycline, and minocycline) should past.
racycline, doxycycline, or minocycline is not be used in children younger than Adapted from Gollnick et al,15 Leyden,50 and Del Rosso and
benign intracranial hypertension (BIH), 8 years of age. (SOR: B). Kim.70
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of acne as a topical agent is not believed tretinoin use in acne treatment of sociation between excessive intake of
to be related to P acnes reduction.91 adolescents and preadolescents and vitamin A with the incidence of frac-
Recently, a 5% dapsone gel was ap- agrees that it may be used in younger tures. In evaluating isotretinoin spe-
proved in the United States for acne patients with severe, refractory, and cifically, 1 small prospective cohort
treatment. It was evaluated in two 12- scarring acne. study associated isotretinoin with
week randomized, double-blind, phase Its most common side effects include minimal-to-mild bone demineralization
3 trials in patients aged 12 and older dry, chapped skin and lips, dry eyes, and at specific sites (such as Ward’s tri-
with mild, moderate, or severe acne.92 myalgias. Nose bleeds secondary to angle of the femur), but revealed that
The 3010 subjects used dapsone 5% dryness also are common. These effects these effects may be reversible.113 Ad-
gel twice daily or vehicle gel. A com- are generally reversible upon discon- ditional data from small prospective
bined analysis revealed a statistically tinuation of the drug. Some patients cohort114 and case control studies115,116
significant reduction in noninflam- may experience increases in serum have, however, documented no mea-
matory and inflammatory lesions by triglycerides and changes in liver surable changes in bone mineralization
week 12 compared with vehicle (P , enzymes. Both fasting serum lipids and markers. These changes were not as-
.001). Treatment response was rapid, liver function tests should be obtained sociated with increased risk of frac-
with statistically significant inter- at baseline and monitored periodically tures in those treated with isotretinoin
group differences in lesion count at thereafter. A major adverse effect of at the standard doses and durations
4 weeks. Adverse events were com- isotretinoin and a public health concern used for acne.
parable between dapsone gel and is its teratogenic potential. For this Hyperostoses are thought to occur with
vehicle gel and rarely led to discon- reason, the FDA mandated in 2007 the somewhat greater frequency among
tinuation. implementation of a computerized risk those who received long-term systemic
Available studies demonstrate that management program (iPledge), which retinoid therapy for disorders of kera-
topical dapsone is most effective registers all isotretinoin patients, phy- tinization. Hyperostosis during retinoid
against inflammatory lesions, with ef- sicians, pharmacies, and manufac- use has been most strongly associated
ficacy enhanced more when combined turers and ensures monthly monitoring with long-term therapy or chemo-
with a topical retinoid as compared of pregnancy status in females of prevention, appears to be dose- and
with BP.92,93 The safety of 5% dapsone childbearing potential. duration-dependent, is often asymp-
gel applied twice daily has been dem- Three of the most significant and con- tomatic, and may resolve spontane-
onstrated in patients who are glucose troversial groups of adverse effects ously. Overall, this phenomenon
6 phosphate dehydrogenase-deficient attributed to isotretinoin and de- appears to be uncommon among those
and in patients who are sulfonamide scribed in the drug’s package insert receiving isotretinoin for acne vulgaris.
allergic.94–96 The most common application- are skeletal issues; potential for de- Premature epiphyseal closure in as-
site reactions consisted of erythema velopment of inflammatory bowel sociation with retinoid therapy appears
and dryness that were similar be- disease (IBD); and mood changes, de- to be a rare event and may occur in an
tween groups. A temporary orange pression, suicidal ideation, and sui- asymmetric or generalized fashion.
staining of the skin can occur when cide, which are addressed in greater Only a single case has been reported in
BP and topical dapsone are used detail because of their relevance in association with isotretinoin adminis-
together. pediatric patients.98 tered for acne.117 Other cases have
primarily been reported as a conse-
Oral Isotretinoin in Severe Acne Bone Effects quence of isotretinoin therapy for
disorders of keratinization118 or neu-
Oral isotretinoin targets all of the The interaction between retinoids and
roblastoma.113,119
pathophysiologic factors involved in skeletal homeostasis is complex. Ani-
acne typically producing excellent mal studies have indicated that exces-
results.15 A recent consensus con- sive intake of retinoids can have IBD
ference on its use recommends inhibitory effects on both osteoblast There are conflicting data on the po-
a starting dose of 0.5 mg/kg per day and osteoclast activity that may pose tential association between isotretinoin
for the first 4 weeks to avoid initial a theoretical risk for fractures or hy- and IBD. In available published reports,
flares, increasing to the full dosage of perostosis.99–112 Well-designed clinical 21 patients with preexisting IBD who
1 mg/kg per day.97 The panel concurs studies involving human subjects have subsequently receive isotretinoin have
with this recommendation for iso- generated conflicting data on the as- been reported to tolerate the drug;
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and older as outlined in Table 7. All of the duction and blocking the effects of The most important issues regarding
products are pregnancy category C. androgens on the sebaceous gland that the use of combination OCs in the pe-
In the phase 3 pivotal trials for BP 2.5%/ leads to reduction of sebum production diatric population involve whether low
clindamycin 1.2% gel (Acanya, Coria and improvement in acne. Combination doses of estrogen provide sufficient
Laboratories), 62% of enrolled patients oral contraceptives (OCs; estrogen plus estrogen for bone accrual and at what
were between the ages of 12 and 17. In progestin) block the ovarian production age it is safe to initiate use. Approxi-
a subanalysis of 12- to 17-year-old of androgen, and antiandrogens, such mately 50% of bone mass is accrued
patients, lesion count and success as spironolactone, block the effects of between the ages of 12 and 18 years.142
rate were similar to those obtained in androgens on the sebaceous gland. In Some experts believe that it is impor-
the study as a whole.139 In the pivotal patients diagnosed with congenital tant to allow the development of as
trial for tretinoin 0.025%/clindamycin adrenal hyperplasia, low-dose gluco- much bone mineral density (BMD) as
1.2% (Ziana Gel, Medicis Pharmaceuti- corticoids are used to suppress the possible before initiating treatment
cal Corporation, Scottsdale, AZ), 51% of adrenal production of androgens. with exogenous estrogen.
enrolled patients were 12 to 17 years of Although others have antiacne efficacy, In a 24-month study of postmenarchal
age and, in an unpublished subanalysis only 3 combination OCs are currently FDA girls with a mean age of 16.0 6 1.4
for the pediatric age group, was es- approved for the treatment of acne years who were treated with an OC
sentially no different from the study (Ortho Tri Cyclen [norgestimate/ethinyl containing 100 mcg levonorgestrel and
group as a whole. In the BP 2.5%/ estradiol] Tablets indicated for use in 20 mcg ethinyl estradiol, there was
adapalene 0.1% gel (Epiduo Gel, moderate acne in females $15 years a mean increase in lumbar spine BMD
Galderma Laboratories, LP, Fort Worth, of age; Estrostep [norethindrone acetate at the femoral neck in 4.2% of girls who
TX) pivotal trial, the mean age was 16.2 and ethinyl estradiol] Tablets indi- received OC versus 6.3% in untreated
years and a subanalysis of results in cated for use in moderate acne for controls.143 The use of OCs did not re-
the 12- to 17-year-old group was simi- females $15 years of age; and Yaz sult in osteopenia in any subject. Nev-
lar to the study group as a whole.140 [drospirenone/ethinyl estradiol] Tablets ertheless, the authors concluded that it
Although sometimes more costly than for moderate acne in females $14 years is unclear whether the currently
single agents prescribed separately, of age). The reduction in the estrogen available low-dose OC containing 20
fixed combinations applied once daily dosage of OCs has lowered the risk of mcg ethinyl estradiol is adequate for
are very convenient and thus may im- thromboembolism associated with some bone mass accrual in this age group. A
prove adherence.52,141 of the earlier OC formulations, although long-term study of combined OCs with
this relationship is still under review by calcium supplementation revealed no
Consensus Recommendation:
the FDA. Although absolute thromboem- effect on BMD after 10 years.144 Re-
Fixed-dose combination topical ther- bolic risk is low in adolescence, it is ferral to an adolescent medicine spe-
apies may be useful in regimens of recommended that a family history of cialist or gynecologist for management
care for all types and severities of thrombotic events be obtained and of OC treatment remains dependent on
acne. (SOR adolescents: A; preado- young patients are asked if they smoke the physician’s comfort level.
lescents and younger: B). before OCs are prescribed. The most Spironolactone is a synthetic steroidal
common adverse events related to their androgen receptor blocker that is often
HORMONAL THERAPY use include nausea/vomiting, breast used in female acne patients.145,146 In
Hormonal therapy in acne is directed at tenderness, headache, weight gain, and select groups of acne patients, spi-
suppressing ovarian androgen pro- breakthrough bleeding. ronolactone has revealed efficacy,147–149
although its overall role in acne therapy
and appropriate age to initiate treat-
TABLE 7 Topical Fixed-Dose Combination Prescription Acne Therapies ment has not yet been fully deter-
Product Active Ingredients and Concentration mined.150 There are minimal data on its
Acanya Gel Clindamycin phosphate, 1.2%; BP, 2.5% (aqueous-based) use in pediatric acne.
BenzaClin Gel (generic available) Clindamycin phosphate, 1%; BP, 5% (aqueous-based)
Benzamycin Gel (generic available) Erythromycin, 3%; BP, 5% (alcohol-based) Consensus Recommendations:
Duac Gela Clindamycin phosphate, 1%; BP, 5% (aqueous-based) Hormonal therapy with combined
Epiduo Gel Adapalene, 0.1%; BP, 2.5%
Veltin Gel Clindamycin phosphate, 1.2%; Tretinoin, 0.025% OC may be useful as second-line
Ziana Gel Clindamycin phosphate, 1.2%; Tretinoin, 0.025% therapy in regimens of care in pu-
a Duac Gel is indicated for inflammatory acne vulgaris. bertal females with moderate-to-
severe acne. Tobacco use and family Because of concerns about growth acne unassociated with endocrino-
history of thrombotic events should and bone density, many experts logic pathology until 1 year after
be assessed. (SOR adolescents: A). recommend withholding OC for onset of menstruation. (SOR: C).
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FIGURE 2
Pediatric treatment recommendations for moderate acne.
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EVIDENCE-BASED TREATMENT antibiotics, and BP as individual decades. Physicians may elect to initiate
RECOMMENDATIONS FOR agents or fixed-dose combinations. treatment of moderate acne with
PEDIATRIC ACNE (SOR adolescents: A; SOR preado- a topical regimen and add an oral an-
lescents and younger: B). tibiotic if the therapeutic response is
When selecting acne treatment, it is
not adequate. Alternatively, an oral
important to assess severity as a func-
Inadequate Response antibiotic may be started concomitantly
tion of number, type, and severity of
lesions as well as psychological impact If response to first-line treatment is with a topical regimen for moderate-to-
inadequate, it is important to check severe acne. Optimally, the topical
on the patient including the likelihood of
adherence by asking the patient and/or regimen would include a retinoid and
scarring and/or dyspigmentation. The
the parent and, if necessary, to reiterate a BP-containing formulation, either
panel recommends pediatric treatment
usage instructions. If adherence ap- separately or as a combination product.
recommendations based on severity of
pears to be adequate, a topical retinoid In addition, use of an oral antibiotic may
mild, moderate, and severe acne as
or BP may be added to monotherapy be especially prudent if there is evi-
discussed later.
with either agent. It has been shown dence of acne scarring, even if the
that early initiation of clindamycin/BP + current severity of inflammatory acne
Mild Acne is more modest.151 Importantly, some
adapalene produced earlier and greater
Mild acne may present as pre- reductions in lesion counts when com- oral antibiotics, especially tetracycline
dominantly comedonal or as mixed pared with adapalene monotherapy or derivatives, in addition to antibiotic
comedonal and inflammatory disease BP/clindamycin for 4 weeks, with ada- activity against P acnes, exhibit certain
(Fig 1). Evidence-based treatment rec- palene added at week 4.152 The con- antiinflammatory and immunomodu-
ommendations by the panel for mild centration, type, and/or formulation latory properties that may be operative
acne are highlighted in Fig 1. of the topical retinoid may be changed, in counteracting mechanisms or path-
or the topical combination therapy ways involved in acne lesion de-
Initial Treatment can be changed. Another option to velopment.60,153–155
Topical therapy alone or in combination consider is topical dapsone; however, Typically, 4 to 8 weeks of compliant oral
is recommended as initial treatment of the panel notes large-scale compara- antibiotic use are needed before the
mild acne. BP as a single agent, topical tive studies of dapsone versus other clinical effects of an oral antibiotic are
retinoids, or combinations of topical topicals are lacking, particularly in pe- visible, whereas maximal response may
retinoids, antibiotics, and BP as in- diatric patients. require 3 to 6 months of administra-
dividual agents or fixed-dose combi- tion.15,70 Once the formation of new in-
nations may be used. Moderate Acne flammatory lesions, defined as lesions
In patients of color in whom the pro- Although it is recommended to start that are raised by palpation, are
pensity for scarring and PIH is greater, with the least aggressive, effective markedly diminished in number, con-
initial treatment also might include an regimen, moderate (Fig 2) and severe sideration may be given to stopping
oral or topical antibiotic.151 Depending acne typically requires a more ag- oral antibiotics with continuation of
on patient and parent preference, gressive regimen, possibly with the topical therapy to maintain control of
treatment could be initiated with addition of oral antibiotics (Fig 3). acne.
monotherapy, including OTC products. Consensus Recommendation:
OTC products are generally effective for Initial Therapy Moderate acne may be initially
very mild acne, but, with the exception Initial therapy for moderate acne may treated with topical combinations
of BP, data on the efficacy of their include topical combination therapies including a retinoid and BP and/
ingredients are lacking. Patients as described earlier or with combina- or antibiotics, or with oral antibiot-
should be counseled that it takes ∼4 to tions that include topical dapsone. ics in addition to a topical retinoid
8 weeks to demonstrate visible results and BP and/or topical antibiotics.
from any acne treatment. Adding an Oral Antibiotic (SOR adolescents: A; SOR preado-
Consensus Recommendation: Overall, oral antibiotic therapy is a safe lescents and younger: C).
Initial therapy for mild acne may and effective approach to the treatment
include OTC products such as BP of moderate-to-severe inflammatory or Inadequate Response
as a single agent, topical retinoids, mixed comedonal and inflammatory If response to the above topical com-
or combinations of topical retinoids, acne vulgaris used for more than 5 bination regimens with or without oral
S180 EICHENFIELD et al
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SUPPLEMENT ARTICLE
52% after 3 months.159 Adherence may age, disease severity, social and familial Diet and Acne
be improved through patient and parent networks, and individual personalities. Consideration of a role for diet in con-
education, selection of a simple regi- Adolescents with substantial acne are tributing to acne arose in the 1930s, and
men, more frequent doctor visits, and reported to have high rates of mental chocolate, sugar, and iodine were
choice of vehicles that improve medica- health problems, affective isolation, among the dietary factors implicated.
tion tolerability. One study revealed a di- social impairment, depression, and As a result of a series of studies in the
rect correlation between adherence and suicidal ideation.162 In the cases where late 1960s that failed to identify a dietary
dosing frequency, with 83.6% of patients the impact on the psychosocial health connection, the concept fell out of
complying with once-daily dosing versus of the patient is particularly burden- fashion.164 However, the debate has
74.9% with twice-daily dosing. Fixed some, effective treatment of acne may been rekindled in response to a variety
combinations of topical medications result in improvements in self-esteem, of data emerging over the last decade.
may be helpful in this regard. affect, shame, embarrassment, body
A retrospective recall-based study in
Empowering patients with control over image, social assertiveness, and self-
adult nurses165 and a prospective self-
their care is important for adher- confidence.150
assessment study in teenage girls166
ence.160 It is essential to elicit informa- both suggested an association be-
tion at each doctor visit about patient Managing Expectations tween acne and intake of milk and
preferences and lifestyle. For example, other dairy products. A subsequent
Adolescents are notoriously impatient.
a water-based gel may be the optimal prospective study in teenage boys
Physicians, who see the patient at
choice for the patient who wears suggested an association with skim
intervals rather than daily, may note
makeup.161 Teenagers, especially males, milk,167 although the previous 2 studies
improvement between visits that may
may not like the feel of moisturizers but did not identify a difference based on
not be readily apparent to the adoles-
may accept a gel, pad or foam, or in- milk fat content.
cent who examines his or her face in the
shower wash.160 Other vehicle consid-
mirror several times per day.156 A basic The effects on acne of glycemic load in
erations center around tolerability,
understanding of acne pathophysiol- the diet also have been subjected to
which is influenced by the medication’s
ogy and how prescribed agents work examination. An anthropologic study168
impact on the skin barrier. Many topical
to control acne may augment adher- comparing acne rates in a hunter-
medications are being formulated in
ence.163 For example, both patients and gatherer population in Papua New
vehicles, including aqueous gels, which
parents should be given reasonable Guinea versus those in the developed
are therapeutic and may help rehydrate
expectations of the time to visible im- world suggested that dietary glycemic
and repair the skin barrier.161 It may be
provement. It is important to explain load may contribute to the observed
useful to initiate treatment with ex-
that acne may worsen or irritation may differences in acne incidence. A num-
tremely mild topical agents until the
be more significant initially, with gradual ber of prospective trials169,170 sub-
skin has adjusted to medication effects
improvement. An understanding of the sequently have been performed,
and patients have adapted to side
“invisible microcomedo” helps patients notably including a randomized pro-
effects.160
understand why topical medications spective controlled trial of a low gly-
should be applied to the entire face. cemic diet versus a high glycemic diet
Active Scarring
Many adolescents believe that acne is in teenage boys.171 By the end of the
The likelihood of scarring is an im- related to facial hygiene, and so they 12-week study, the low glycemic diet
portant consideration in treatment may try treating themselves with harsh was shown to provide superior reduc-
selection. Patients with moderate and astringents, abrasives, or vigorous tion in the number of total acne lesions
severe acne are at increased risk of scrubbing. It is important for them to (223.5 6 3.9 vs 212.0 6 3.5, P = .03),
scarring, as are those with more deeply understand that such treatment may as well as reductions in inflammatory
pigmented skin.151 Hence, aggressive actually worsen theiracne and increase lesion count and other parameters in-
treatment is warranted to prevent the likelihood of inflammation and cluding weight and BMI.
permanent sequelae in these patient scarring. Many clinicians prefer to rec- Other dietary constituents that are the
populations. ommend an appropriate gentle, daily subject of renewed interest include zinc
skin-care regimen, including a non- and antioxidants; the role of chocolate
Psychosocial Impact comedogenic moisturizer and sun- is being reinvestigated in a blinded
The psychosocial impact of acne is in- screen for the patient to use with the placebo-controlled clinical trial (clin-
fluenced by numerous factors including prescribed treatment(s). icaltrials.gov). Based on the currently
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ABBREVIATIONS
AARS—American Acne and Rosacea Society
BIH—benign intracranial hypertension
BMD—bone mineral density
BP—benzoyl peroxide
DHS—drug hypersensitivity syndrome
FDA—Food and Drug Administration
IBD—inflammatory bowel disease
LLS—lupuslike syndrome
NCP—neonatal cephalic pustulosis
OC—oral contraceptive
OTC—over-the-counter
PCOS—polycystic ovary syndrome
PIH—postinflammatory hyperpigmentation
SOR—Strength of Recommendation
www.pediatrics.org/cgi/doi/10.1542/peds.2013-0490B
doi:10.1542/peds.2013-0490B
Accepted for publication Feb 21, 2013
Address correspondence to Lawrence F. Eichenfield, MD, 8010 Frost Street, Ste 602, San Diego, CA 92130. E-mail: leichenfield@rchsd.org
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: All authors filed relevant conflicts of interest statements with the American Acne and Rosacea Society (AARS) and the American Academy
of Pediatrics (AAP). They received compensation from the AARS for participation in this consensus conference. Their participation included preparatory
conference calls, planning communications, extensive literature search and research on subject, preparation of presentations including slides, and manuscript
development, writing, and editing. No corporate benefactor of the AARS or AAP had any input into content preparation, data review, or any involvement in the
outcome of the meeting or publication. Physician Resources, LLC provided editorial and research assistance to the AARS throughout the process.
FUNDING: The AARS, a nonprofit organization, received educational grant funding from annual corporate benefactors to fund this article. Those benefactors
include Galderma Laboratories, Medicis Pharmaceuticals, Ortho Dermatologics, and Valeant Pharmaceuticals. No corporate benefactor of the AARS or AAP had any
input into content preparation or data review, or any involvement in the outcome of the meeting or publication.
S186 EICHENFIELD et al
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Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric
Acne
Lawrence F. Eichenfield, Andrew C. Krakowski, Caroline Piggott, James Del Rosso,
Hilary Baldwin, Sheila Fallon Friedlander, Moise Levy, Anne Lucky, Anthony J.
Mancini, Seth J. Orlow, Albert C. Yan, Keith K. Vaux, Guy Webster, Andrea L.
Zaenglein and Diane M. Thiboutot
Pediatrics 2013;131;S163
DOI: 10.1542/peds.2013-0490B
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