evidence-based recommendations for the diagnosis...

Evidence-Based Recommendations for the Diagnosisand Treatment of Pediatric Acne

abstractINTRODUCTION: Acne vulgaris is one of the most common skin con-ditions in children and adolescents. The presentation, differential di-agnosis, and association of acne with systemic pathology differs byage of presentation. Current acknowledged guidelines for the diag-nosis and management of pediatric acne are lacking, and there arevariations in management across the spectrum of primary and spe-cialty care. The American Acne and Rosacea Society convened a panelof pediatric dermatologists, pediatricians, and dermatologists withexpertise in acne to develop recommendations for the managementof pediatric acne and evidence-based treatment algorithms.

METHODS: Ten major topic areas in the diagnosis and treatment ofpediatric acne were identified. A thorough literature search was per-formed and articles identified, reviewed, and assessed for evidencegrading. Each topic area was assigned to 2 expert reviewers who de-veloped and presented summaries and recommendations for critiqueand editing. Furthermore, the Strength of Recommendation Taxonomy,including ratings for the strength of recommendation for a body ofevidence, was used throughout for the consensus recommendationsfor the evaluation and management of pediatric acne. Practicalevidence-based treatment algorithms also were developed.

RESULTS: Recommendations were put forth regarding the classifica-tion, diagnosis, evaluation, and management of pediatric acne, basedon age and pubertal status. Treatment considerations include the useof over-the-counter products, topical benzoyl peroxide, topicalretinoids, topical antibiotics, oral antibiotics, hormonal therapy, andisotretinoin. Simplified treatment algorithms and recommendationsare presented in detail for adolescent, preadolescent, infantile, andneonatal acne. Other considerations, including psychosocial effectsof acne, adherence to treatment regimens, and the role of diet andacne, also are discussed.

CONCLUSIONS: These expert recommendations by the American Acneand Rosacea Society as reviewed and endorsed by the American Acad-emy of Pediatrics constitute the first detailed, evidence-based clinicalguidelines for the management of pediatric acne including issues ofspecial concern when treating pediatric patients. Pediatrics 2013;131:S163–S186

AUTHORS: Lawrence F. Eichenfield, MD,a Andrew C.Krakowski, MD,a Caroline Piggott, MD,a James Del Rosso,DO,b Hilary Baldwin, MD,c Sheila Fallon Friedlander, MD,a

Moise Levy, MD,d Anne Lucky, MD,e Anthony J. Mancini, MD,f

Seth J. Orlow, MD, PhD,g Albert C. Yan, MD,h Keith K. Vaux,MD,i Guy Webster, MD, PhD,j Andrea L. Zaenglein, MD,k,l andDiane M. Thiboutot, MDl

aDivision of Pediatric and Adolescent Dermatology, RadyChildren’s Hospital, San Diego and Departments of Pediatrics andMedicine (Dermatology), University of California, San Diego, SanDiego, California; bSection of Dermatology, Valley HospitalMedical Center, Las Vegas, Nevada; cDepartment of Dermatology,SUNY Downstate Medical Center, Brooklyn, New York; dPediatric/Adolescent Dermatology, Dell Children’s Medical Center, Austin,Texas, Department of Dermatology, UT Southwestern MedicalSchool, Dallas, Texas and Departments of Pediatrics andDermatology, Baylor College of Medicine, Houston, Texas;eDepartments of Dermatology and Pediatrics, University ofCincinnati College of Medicine and Cincinnati Children’s HospitalMedical Center, Cincinnati, Ohio; fDepartments of Pediatrics andDermatology, Northwestern University Feinberg School ofMedicine and Division of Dermatology, Ann & Robert H. LurieChildren’s Hospital of Chicago; gThe Ronald O. PerelmanDepartment of Dermatology, New York University School ofMedicine, New York, New York; hSection of Pediatric Dermatology,Children’s Hospital of Philadelphia, Philadelphia, Pennsylvaniaand Departments of Pediatrics and Dermatology, PerelmanSchool of Medicine at the University of Pennsylvania;iDivision of Pediatrics and Hospital Medicine, Rady Children’sHospital, San Diego, California and Department of Pediatrics,University of California, San Diego, California; jDepartment ofDermatology, Jefferson Medical College, Thomas JeffersonUniversity, Philadelphia, Pennsylvania; kDepartment ofDermatology, The Pennsylvania State University College ofMedicine; and lDepartment of Pediatrics, Penn State HersheyChildren’s Hospital, Hershey, Pennsylvania

KEY WORDSpediatric acne, acne treatment, combination acne therapy,retinoids, benzoyl peroxide, bacterial resistance, isotretinoin,hormonal therapy, acne guidelines, acne algorithm, neonatalacne, infantile acne, mid-childhood acne, preadolescent acne,American Acne and Rosacea Society, AARS

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PEDIATRICS Volume 131, Supplement 3, May 2013 S163

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Acne vulgaris is one of the most com-mon skin conditions in children andadolescents. Although often considereda disease of teenagers, in whom theprevalence is reported to be from 70%to 87%,1 12 years of age is no longerconsidered the lower end of the agerange for acne onset.2 A study by Luckyet al3 revealed acne lesions in 78% of365 girls ages 9 to 10. In addition, acneand other acneiform (acnelike) con-ditions occur at different ages, in-cluding neonates, infants, and youngchildren, and may be associated withdifferential diagnoses or systemic pa-thology that differs from teenagers.

There are issues of special concern intreatment of preadolescents with acne.The majority of clinical trials for acnemedications are conducted in patients12 years of age or older. As a result,there is little published evidence re-garding the safety and efficacy of manyacne medications in pediatric patients.Furthermore, the treatment of acneoften involves use of several medi-cations that targeteitherdifferent typesof acne lesions, different factors in-volved in the pathogenesis of acne, ordifferent degrees of acne severity. Po-tential interactions between medi-cations can add another layer ofcomplexity to the management of acnein pediatric patients, as can concernsabout systemic side effects and impactof medications on growth and de-velopment. The psychosocial impact ofacne can be significant, as can issues ofadherence to treatment regimens.

Currently, detailed, acknowledged guide-lines for the diagnosis and manage-ment of acne in pediatric patients arelacking. Recognizing the need to ad-dress special issues regarding thediagnosis and treatment of acne inchildren of various ages, a panel ofexperts consisting of pediatric der-matologists, pediatricians, and der-matologistswith expertise in acnewasconvened under the auspices of the

American Acne and Rosacea Society,a nonprofit organization promotingresearch, education, and improvedcare of patientswith acne and rosacea.The expert panel was charged withdeveloping recommendations for themanagement of pediatric acne andevidence-based treatment algorithms.Amemberof theexpertpanel servedasliaison to the American Academy ofPediatrics and as part of the recom-mendation writing group.

METHODS

The expert panel identified specialissues in thediagnosis and treatment ofacne and acneiform conditions in pe-diatric patients across various ages.Tenmajor topic areaswere specified bythe panel (Table 1). A thorough English-language literature search was perfor-med for each topic area, and identifiedarticles were reviewed utilizing apatient-centered approach to gradingevidence available to the expert panel.4

Relevant clinical trial registries anddata filed with the Food and Drug Ad-ministration (FDA) were included in thedata review.

Each topic area was assigned to 2 ex-pert reviewers, who developed andpresented an in-depth summary andrecommendations for further critiqueand editing. The Strength of Recom-mendation (SOR) Taxonomy ratings forthe recommendation for a body of evi-dence is noted throughout the article.4

This taxonomy addresses the quality,quantity, and consistency of evidenceand allows authors to rate individualstudies or bodies of evidence. The tax-onomy emphasizes the use of patient-oriented outcomes that measurechanges in morbidity or mortality. Theauthors reviewed the bodies of evi-dence for each of the recommenda-tions and assigned one of the followingSOR: an A-level recommendation isbased on consistent and good-qualitypatient-oriented evidence; a B-levelrecommendation is based on inconsis-tent or limited-quality patient-orientedevidence; and a C-level recommenda-tion is based on consensus, usualpractice, opinion, disease-oriented ev-idence, or case series for studies ofdiagnosis, treatment, prevention, orscreening. This article summarizes theresultant consensus recommenda-tions for the evaluation and diagnosisof pediatric acne, as well as a series oftreatment algorithms to assist healthcare practitioners in the managementand treatment of acne in pediatricpatients.

CATEGORIZATION ANDDIFFERENTIAL DIAGNOSIS OFPEDIATRIC ACNE

Both age and form of presentation arerelevant to the diagnosis of pediatricacne. Although there is some overlap inage and presentation of acneiformconditions, the consensus of the panelregarding relevant age categories ispresented in Table 2. These ranges areapproximate. In girls, age of onset ofmenarche may be a better delineatingpoint between preadolescence and

TABLE 1 Topic Areas Researched andDiscussed by Expert Panel

Pediatric Acne Categorization and DifferentialDiagnosis of Acne

Evaluation of Pediatric Acne by Age/ClassificationEvidence-based Treatment Review for PediatricAcne• OTC products• BP treatment• Topical retinoids, antibiotics, and fixed-dosecombination products

• Oral antibiotics: age-related issues, safety, andresistance

• Isotretinoin pediatric patients with severe acne• OC use and hormonal therapy

Pediatric Acne Treatment Considerations• Previous treatment history• Costs• Ease of use/regimen complexity and adherence• Vehicle selection• Active scarring• Side effects• Psychosocial impact• Diet

S164 EICHENFIELD et al



adolescence. In general, acne is un-complicated by systemic disease, butin some cases it may be a cutaneousmanifestation of underlying pathology.It is essential to have a broad un-derstanding of acne at different agesand to be aware of the differential di-agnoses for each age group. Table 3presents a differential diagnosis foracne in each age group.5–7 Workup isbased on age and physical findings.6

The physical examination should focuson type and distribution of acnelesions, height, weight, growth curve,and possible blood pressure abnor-malities. Signs of precocious sexualmaturation or virilization should promptworkup and/or a referral to a pediatricendocrinologist.8

Consensus Recommendation:

� Acneiform eruptions from the neo-natal period through adolescencemay be broadly categorized by ageand pubertal status.

Neonatal Acne

Neonatal acne is estimated to affect upto 20% of newborns.9 The major con-troversy in this age group is whetherthe lesions truly represent acne or oneof a number of heterogeneous pap-ulopustular acneiform conditions typi-cally without comedones, such asneonatal cephalic pustulosis (NCP) ortransient neonatal pustular melanosis.Although rare, some neonates maypresent with androgen-driven come-donal and inflammatory acne.8,10 NCPpustules are usually confined to the

cheeks, chin, eyelids, and forehead, butthe scalp, neck, and upper chest andback may be involved.8 Its pathogene-sis may involve colonization withMalassezia species, a normal com-mensal of infant skin, or may representan inflammatory reaction to a yeastovergrowth at birth.8,10 NCP is typicallymild and self-limited, and reassuringthe parents is usually the only man-agement needed. If lesions are nu-merous, 2% ketoconazole cream mayreduce fungal colonization.11 New-borns alsomay present with or developtransient neonatal pustular melanosis,with pustules on the chin, neck, ortrunk. Within 24 hours, these pustulesrupture, leaving hyperpigmented mac-ules with a rim of faint white scale.10


� Neonates may have true acne, al-though many self-limited papulo-pustular eruptions also occur onthe faces of neonates. In infantsand younger children (,7 yearsof age) with significant acne vulga-ris, evaluation for signs of sexualprecocity, virilization, and/or growthabnormalities that may indicate anunderlying systemic abnormality(endocrinologic diseases, tumors,gonadal/ovarian pathology) and ap-propriate workup and/or referral toa pediatric endocrinologist may bewarranted. (SOR: C).

Infantile Acne

Infantile acnemay begin at∼6 weeks ofage and last for 6 to 12 months or,rarely, for years. It is more common inboys and presents with comedones aswell as inflammatory lesions, whichcan include papules, pustules, or oc-casionally nodular lesions. Physicalexamination should include assess-ment of growth including height,weight, and growth curve; testiculargrowth and breast development; pres-ence of hirsutism or pubic hair; clito-romegaly; and increased muscle

mass.12 Should workup for a hormonalanomaly be considered, a pediatricendocrinology referral and/or boneage and serologic evaluation of follicle-stimulating hormone, luteinizinghormone,testosterone, and dehydroepiandros-terone sulfate levels are recommended.No further workup is necessary for themajority of cases in the absence ofhormonal abnormalities. It is also im-portant to distinguish true infantileacne from other similar cutaneouslesions, because there is some evidencethat infantile acne predisposes to moresevere adolescent acne.13 Infantile acnemay be treated with topical antimicro-bial agents; topical retinoids; noncyclineantibiotics, such as erythromycin; and,occasionally, isotretinoin, though all arewithout FDA indication for use in thisage group.


� Most infantile acne is self-limitedand not associated with underlyingendocrine pathology. However, inpatients with additional physicalsigns of hormonal abnormality,a more extensive workup and/orreferral to a pediatric endocrinol-ogist may be appropriate. (SOR: C).

Mid-Childhood Acne

Mid-childhood acne presents primarilyon the facewithamixtureof comedonesand inflammatory lesions.10 Childrenbetween the ages of 1 and 7 years,however, do not normally producesignificant levels of adrenal or gonadalandrogens; hence, acne in this agegroup is rare. When it does occur, anendocrine abnormality should be sus-pected. A workup by a pediatric endo-crinologist is usually warranted to ruleout adrenal or gonadal/ovarian pa-thology including the presence ofandrogen-secreting tumors. Increasedbone age and accelerated growth, asevidenced by deviation from standard-ized age-appropriate growth curves,are important indicators of the effects

TABLE 2 Expert Panel Consensus: PediatricAcne Categorized by Age

Acne Type Age of Onset

Neonatal Birth to #6 wkInfantile 6 wk to #1 yMid-childhood 1 y to ,7 yPreadolescent $7 to #12 y or menarche

in girlsAdolescent $12 to #19 y or after

menarche in girls

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of excess androgens. In addition to treat-ments to address androgen-secretingtumors or congenital adrenal hyper-plasia, the treatment of mid-childhoodacne is similar to that of adolescentacne except that oral tetracyclines areusually not an option in children younger

than 8 years of age because of the riskof damage to developing bones andtooth enamel. Hormonal therapy couldbe used if warranted by endocrinologicpathology.8


� Mid-childhood acne is very uncom-mon and should warrant an endo-crinologic workup for causes ofhyperandrogenism. (SOR: C).

Preadolescent Acne

It is not uncommon for acne vulgaris tooccur in preadolescents, as a result ofnormal adrenarche and testicular/ovarian maturation. Acne may be thefirst sign of pubertal maturation.8 Infact, with the trend toward earlier ageof onset of adrenarche and menarche,there appears to be a downward shiftin the age at which acne first appears.Preadolescent acne is characterized bya predominance of comedones on theforehead and central face (the so-called “T-zone”) with relatively few in-flammatory lesions.10 Early pre-sentation may include comedones ofthe ear.

History and physical examination arethe most important parts of the as-sessment in this age group. Furtherworkup is generally unnecessary un-less there are signs of excess andro-gens.7 Polycystic ovary syndrome(PCOS) or another endocrinologic ab-normality may be considered when theacne is unusually severe, accompaniedby signs of excess androgens, or isunresponsive to treatment.14 Pelvic ul-trasound is not considered useful fordiagnosis of PCOS because it is non-specific.

Treatment of uncomplicated pre-adolescent acne is comparable to thatof acne in older age groups, as dis-cussed later. It is important in this agegroup to elicit the patient’s level ofconcern regarding his or her acne,which may not always be concordantwith parental concern.


� Preadolescent (7–12 years) acne iscommon and may precede othersigns of pubertal maturation. Workupbeyond history and physical is gen-erally unnecessary unless thereare signs of androgen excess, PCOS,or other systemic abnormalities.(SOR: B).

PEDIATRIC ACNE CLASSIFICATIONAND SEVERITY ASSESSMENT

In general, treatment of pediatric acnevulgaris is similar to acne treatment inolder adolescents and adults and isbased on acne pathophysiology. Thepathogenesis of acne involves the in-terplay of 4 factors: sebaceous hyper-plasia under the influence of increasedandrogen levels, alterations in folliculargrowth anddifferentiation, colonizationof the follicle by Propionibacteriumacnes (P acnes), and consequent im-mune response and inflammation.15

A useful clinical categorization of acneis based on predominate morphology:comedonal with closed and opencomedones (“whiteheads” and “black-heads”); inflammatory, with erythema-tous papules, nodules, or cystlikenodular lesions; or mixed, where bothtypes of lesions are present. The micro-comedo is the not-clinically-apparentprecursor of both comedonal and in-flammatory lesions. It is a product of hy-peractive sebaceous glands and alteredfollicular growth and differentiation.Reduction in existing microcomedonesand prevention of the formation of newones is central to the management ofall acne lesions.16

Comedones form as a result of in-creased cell division and cohesivenessof cells lining the follicular lumen.Whenthese cells accumulate abnormally, mixwith sebum, and partially obstruct thefollicular opening, they form a closedcomedo (whitehead). If the follicularopening is larger, the keratin buildup is

TABLE 3 Differential Diagnosis of Acne inYounger Pediatric and AdolescentPatients

Adolescent (∼12–18 y of age)

Corticosteroid-induced acneDemodex folliculitisGram-negative folliculitisKeratosis pilarisMalassezia (pityrosporum) folliculitisPapular sarcoidosisPerioral dermatitisPseudofolliculitis barbaeTinea faciei

Preadolescent ($7 to #12 y of age)Acne venenata or pomade acne (from the use

of topical oil-based products)Angiofibromas or adenoma sebaceumCorticosteroid-induced acneFlat wartsKeratosis pilarisMiliaMolluscum contagiosumPerioral dermatitisSyringomas

Mid-Childhood (1–7 y of age)Adrenal tumorsCongenital adrenal hyperplasiaCushing syndromeGonadal tumorsOvarian tumorsPCOSPremature adrenarcheTrue precocious puberty

Any AgeAcne venenata or pomade acne (from the use of

topical or oil-based products)Bilateral nevus comedonicusChlorinated aromatic hydrocarbons (chloracne)Corticosteroids (topical, inhaled, and oral)DemodicidosisFacial angiofibromas (tuberous sclerosis)Flat wartsInfections (bacterial, viral, and fungal)Keratosis pilaris

Medication-Induced (anabolic steroids,dactinomycin, gold, isoniazid, lithium, phenytoin,and progestins)MiliaMiliariaMolluscum contagiosumPeriorificial dermatitisRosacea

Adapted from Tom and Friedlander6 and Krakowski andEichenfield.7




more visible and can darken to form anopen comedo (blackhead). Follicularcolonization with P acnes leads to in-flammation via the production of inflam-matory mediators and the formation ofinflammatory papules and pustules.Nodular acne is characterized by apredominance of large inflammatorynodules or pseudocysts and is oftenaccompanied by scarring or the pres-ence of sinus tracts when adjacentnodules coalesce.

Acne severity may be classified clini-callyasmild,moderate, orseverebasedon the number and type of lesions andthe amount of skin involved. Althoughtherearenumerousgradingsystemsbywhich todefineacneseverity, there isnoagreed-upon standard, and interpre-tation is subjective. Many grading sys-tems are most useful for researchpurposes. For clinical purposes, sim-plicity is key. Typically, patients’ as-sessments do not correlate well witheither those of physicians or publishedseverity scales.17 The panel noted thatseverity scales frequently overemphasizeinflammatory lesions. For example, insome research settings, a patientmight be classified as having mildacne because he or she has only a fewinflammatory lesions in the presenceof hundreds of closed comedones. Insuch cases, the patient (and the phy-sician) is more likely to consider hisor her acne to be severe. Determin-ation of severity can be modified byextent of involvement and scarring aswell.

Although some acne may resolve with-out residual changes, inflammatoryacne may result in the formation ofsignificant scars. In darker skin, post-inflammatory hyperpigmentation (PIH)is common. Residual erythema can oc-cur as well. These changes are mostoften reversible but can take manymonths to fully resolve. Recognizingthese as secondary changes is impor-tant when determining the efficacy of

treatment as patients may not recog-nize the improvement or think theyhave scarring. Effective and earlytreatment is essential to preventscarring as well as postinflammatorychanges and to limit the long-termphysical and psychological impact ofacne.

It has been repeatedly demonstratedthat acne canhave a significant adverseimpact on quality of life, and that thelevel of distress may not correlate di-rectly with acne severity.18,19 In 1 study,assessments using several quality oflife instruments revealed deficits foracne patients who did not correlatewith clinical assessments of severity.20

Reported social, psychological, andemotional symptomswere as severe asthose reported by individuals withchronic medical conditions such aschronic asthma, epilepsy, diabetes, andback pain or arthritis. Adolescents, inparticular, may be insecure about theirappearance and vulnerable to peeropinions. Because social functioningand quality-of-life decrements may notcorrelate with disease severity, evenmild acne may be more troubling toyoung patients than they are willing toadmit.21


� Acne can be categorized as pre-dominately comedonal, inflamma-tory, and/or mixed. Presence orabsence of scarring, PIH, or ery-thema should be assessed. Sever-ity may be broadly categorized asmild, moderate, or severe. (SOR: A).

APPROACH TO PEDIATRIC ACNETHERAPY

The therapeutic objectives in acne areto treat as many age-appropriatepathogenic factors as possible by re-ducing sebum production, preventingthe formation of microcomedones,suppressing P acnes, and reducing in-flammation to prevent scarring.

Although no single acne treatment,apart from isotretinoin, addresses all 4pathogenic factors, it is now clear thatmany of the medications traditionallyused to treat acne actually act by morethan 1 mechanism. In addition to tar-geting the largest number of patho-genic factors, the approach to pediatricacne should be to use the least ag-gressive regimen that is effective whileavoiding regimens that encourage thedevelopment of bacterial resistance.Educatingapatient (andparents) aboutreasonable expectations of results anddiscussing management of treatment-related side effects can maximizeboth compliance and efficacy.

Numerous medications are available totreat acne. Design of an effective regi-men is facilitated by an increased un-derstanding of the mechanisms ofaction, the side effect profile, and theindications and contraindications ofkey antiacne agents discussed later.

OVER-THE-COUNTER TREATMENTOPTIONS

Nationwide television commercials andmagazine ads abound with over-the-counter (OTC) products. Although largelyuntested in controlled clinical trials,many of these products are consideredsomewhat effective, particularly forpatients with mild acne. Those whichhave been tested include salicylic acid-containing topical products and manybenzoyl peroxide (BP) products de-scribed in further detail later. Salicylicacid has revealed some efficacy in acnetrials, although when tested head-to-head with other topicals, particularly BP,it is generally less effective.22,23 Nonpre-scription, nonbenzoyl-peroxide-containingproducts appear to be somewhat ef-fective for the treatment of acne, espe-cially mild acne, though there is limitedpublished evidence supporting theirefficacy in the treatment of acne.

Sulfur, sodium sulfacetamide, andresorcinol are active ingredients in

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several OTC dermatology niche prod-ucts. Sulfur exhibits mild antibacterialand keratolytic properties.24 Becauseof sulfur’s distinctive odor, it is oftencombined with sodium sulfacetamideto mask the scent.25 It is often used inadult female acne because of its fa-vorable tolerability.26,27 Resorcinol alsohas mild antimicrobial properties andis typically formulated in a 2% con-centration in combination with 5%sulfur.

One common acne myth is that poorhygiene and improper cleansing causeacne.21,28 The role of facial cleansing inacne is to remove makeup, dirt, andexcess oil.29 Use of the wrong, tooharsh cleanser can disrupt skin bar-rier, increase transepidermal waterloss, encourage bacterial coloniza-tion, promote comedones, and causesymptoms of burning and stinging.30,31

Typically, twice-daily washing with agentle soap-free, pH-balanced cleanseris recommended. Antibacterial washes,other than BP, have not been shown tobe useful in the treatment of acne.

Facial toners can decrease oiliness andremove makeup and traces of dirt. Theyare a common component of severalprepackaged combination acne treat-ment regimens. Patients should be cau-tious not to overuse facial tonersbecausetheycanbeirritating. If irritationoccurs, this will adversely affect thetolerability of acne medications.

Another common acne myth is that useof cosmetics worsens acne. On thecontrary, use of concealing oil-free,noncomedogenic makeup can im-prove patient quality of life anddoes notworsen the severity of acne.32,33 Use ofcosmetics in patients with acne has notbeen shown to delay treatment re-sponse either.

BP has been shown to be the mostwidely studied of OTC products and hasshown to be one of the most versatile,safe, inexpensive, and effective acnetherapies.34,35 Its lipophilic nature per-

mits it to penetrate the stratum cor-neum and enter the pilosebaceous unitwhere P acnes resides. It acts via thegeneration of free radicals that oxi-dize proteins in the P acnes cell wall.It also has been shown to have mildcomedolytic36 and antiinflammatoryproperties.37,38 BP helps limit the de-velopment of P acnes resistance toantibiotics and also provides increasedefficacy in combinationwith retinoids.39,40

So far, antibiotic resistance to BP hasnot been reported.41–44

Although issues regarding genotoxicityhavebeenraised in thepast, BPhasnowbeen labeled as “GRASE” (generallyregarded as safe and effective) by theFDA, and all topical monotherapyproducts have beenmade available OTCsince 2011. Labeling includes advice toavoid the eyes, lips, and mouth. Theproduct can cause bleaching of hairand clothing, and risk of increasedsunburn and the need for photo-protection also are mentioned. BP fre-quently causes dryness, erythema, andpeeling upon initiation of treatment.Starting with lower concentrations (eg,2.5%) and utilizing more emollientvehicles if needed can help alleviatethese discomforts. Allergic contactdermatitis to BP occurs in 1 in 500people and should be considered ifa patient complains of itching andswelling of the eyes.

BP is available in a variety of for-mulations and in concentrations rang-ing from 2.5% to 10%. There is someevidence that higher concentrations donot increase efficacy but are more ir-ritating. However, the back may bea “special site” circumstance, whereincreasing concentration or prolongedcontact leads to increased efficacy.45

Formulations include a variety of topi-cal leave-on preparations as well aswashes that permit patients to removeBP from the skin, reducing the possi-bility of bleaching of clothing, bedding,or towels.38 It has been suggested that

short-contact BP therapies do not sig-nificantly reduce bacterial load, but dataare lacking. However, they can be effec-tive if left on the skin for the durationrecommended by the manufacturer.

Consensus Recommendations:

� BP is generally regarded as a safeand effective medication that maybe used as monotherapy or in top-ical combination products for mildacne or in regimens of care foracne of all types and severities.(SOR: A).

� BP may minimize development ofantibiotic-resistant P acnes whenused with topical or systemic anti-biotics. (SOR: C).

PRESCRIPTION TREATMENTOPTIONS: SINGLE AGENTS

Topical Retinoids

Topical retinoids, as monotherapy andin topical combination products, areused routinely for the treatment of acnevulgaris. Their safety and efficacy arewell documented in large pivotal trialsthat includedpediatricpatients rangingfrom 12 to 18 years of age. Sub-sequently, because acne routinelypresents in patients younger than 12years of age, topical retinoids arewidely used off-label in this age group.Tretinoin gel 0.05% (Atralin, Coria Lab-oratories, Fort Worth, TX) is FDA-approved foruse inchildren$10 yearsofage,46 and adapalene and benzoyl per-oxide gel 0.1%/2.5% (Epiduo, GaldermaLaboratories, LP, Fort Worth, TX) is in-dicated for ages 9 and older. Adapalenegel, tretinoin gel, and tretinoin micro-sphere gel have been investigated inboth open-label and blinded studies inchildren under 12 years of age.47–49

Retinoids normalize desquamation ofthe follicularepithelium, thuspreventingthe formation of new microcomedones,precursors to both comedonal and in-flammatory lesions, and also promotetheclearingof existingmicrocomedones.50




In addition, some topical retinoidsalso have direct antiinflammatoryactivity.43,51,52 At present, 3 topicalretinoids (tretinoin, adapalene, andtazarotene) are available by pre-scription in the United States. Each isavailable in a variety of formulationsand concentrations (Table 4).53 Theirmost common adverse effects includeburning, stinging, dryness, and scal-ing.15 These effects may be reduced byinitiating treatment with the loweststrength, typically sufficient to treatmild acne, or by recommending regularuse of a moisturizer. Patients should beinstructed not to spot-treat but rather touse a pea-size amount to cover the en-tire face. In patients with sensitive skin,therapy can be initiated with thrice-weekly application, increasing to dailyuse as tolerated.48

Tolerability may be further improved bythe use of a noncomedogenic moistur-izer that includes a sunscreen.15,38 Top-ical tretinoin was the first retinoidapproved for use in the United States. Itis available in a variety of vehicles suchas a micronized gel or a polymerizedcream for increased tolerability. In a12-week open-label study of 40 patientswith mild/moderate acne ages 8 to 12years (mean age, 10.7 years), tretinoinmicrosphere gel 0.04% produced a sig-nificant decrease in Evaluator’s GlobalSeverity Score (P, .001) from baselineto week 12, with 75% of participantsgraded as almost clear or mild. Skinirritation occurred in 35% of thepatients but wasmild inmost cases andimproved by study’s end.48

Other topical retinoid alternativesto tretinoin include adapalene andtazarotene. Adapalene, a distinct reti-noid that is generally well tolerated, isavailable in cream, gel, and lotionformulations.53,54 Adapalene is photo-stable, including in fixed-combinationwith BP.55

Although studies regarding the use oftopical retinoids in pediatric patients

are extremely rare in the literature, ina 16-week study of 12 infants with in-fantile acne (mean age, 12.6 months),0.1% adapalene cleared both come-donal and inflammatory lesions inamedian of 3.4monthswith side effectsthat did not require discontinuation,underscoring the reported high toler-ability of adapalene.47 Tazarotene is aneffective topical retinoid, but it is usedless often as a first-line agent for acnebecause of concerns regarding tolera-bility; it is also known to be more irri-tating.56

In the absence of significant systemicabsorptionof theactive ingredients, thepossibility of intolerability remains theprimary safety issue. However, oldergirls who may be of childbearing po-tential are often of the age grouptreated with topical retinoids. Naturallycirculating endogenous retinoids arepresent in theplasmaof normal healthygirls as a result of dietary consumptionof foods such as fish, carrots, sweetpotatoes, and red peppers. Continuousdaily dosing of tretinoin 0.1% cream,tazarotene 0.1% gel, and adapalene0.1% gel has been shown to only slightlyincrease the mean maximum plasmalevels of circulating retinoids in mostpatients. In 1 study, serum retinoidlevels were found to be more heavilyinfluenced by dietary intake than bytopical application of tretinoin. In

a study of 215 women accidentally ex-posed to topical tretinoin during thefirst trimester of pregnancy, Jick et al57

showed no difference in developmentalanomalies compared with 430 age-matched controls. Tretinoin and ada-palene have a pregnancy category Cand tazarotene a category X rating.


� Topical retinoids (tretinoin, adapa-lene, tazarotene) may be used asmonotherapy or in combinationproducts and in regimens of carefor all types and severities of acnein children and adolescents of allages. (SOR adolescents: A; SOR pre-adolescents and younger: B).

Antibiotics/Antimicrobials

Although acne is not an infection,antibiotics reduce P acnes colonizationof the skin and follicles. They are ef-fective in acne both by inhibiting bac-terial protein synthesis38 and bydecreasing inflammation via inhibitionof bacterial proinflammatory media-tors and decreasing neutrophil che-motaxis.58,59

The alarming increase in P acnes re-sistance to both topical and systemicantibiotics used to treat acne not onlyrenders these drugs less effectiveagainst acne but may also influencecommensal bacteria in both the acne

TABLE 4 Formulations and Concentrations of Topical Retinoids

Retinoid Formulationa Strength, % Pregnancy Category

Tretinoin Cream 0.025, 0.05, 0.1 CGel 0.01, 0.025Gel (micronized) 0.05Microsphere gel 0.04, 0.1Polymerized cream 0.025Polymerized gel 0.025

Adapalene Cream 0.1 CGel 0.1, 0.3Solution 0.1Lotion 0.1

Tazarotene Gel 0.05, 0.1 XCream 0.05, 0.1

Adapted from Imahiyerobo-Ip and Dinulos.52a Numerous generic retinoids are available. Branded products are available under the following trade names: Atralin, Avita,and Retin-A Micro for tretinoin; Differin for adapalene; and Tazorac for tazarotene.

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patient and his or her environment.60

Resistance may occur with both ap-propriate and incorrect use of anti-biotics.58

Topical Antibiotics

Topical antibiotic monotherapy is notrecommended because of both its slowonset of action and the greater likeli-hood of the development of bacterialresistance. If topical or oral antibiotictreatment is to be prolongedmore thana few weeks (as is usually the case inacne treatment), topical BP should beadded to optimize efficacy via its non-specific antimicrobial activity and re-duce the emergence of less sensitiveP acnes variants.60 It has even beensuggested that, if antibiotic therapy ismaintained for more than 3 months,a BP washout should occur betweencourses, although no large studieshave addressed this recommenda-tion.15

Use of topical antibiotics in fixed-combination products containing BPmay help reduce the emergence ofantibiotic-resistant strains of bacteria.In the case of the fixed-combination oftretinoin and clindamycin, concomitantuse of BP is recommended.


� Topical antibiotics (clindamycin,erythromycin) are not recommen-ded as monotherapy because ofslow onset of action and predictableemergence of antibiotic-resistantbacterial organisms. (SOR: C). Iftopical antibiotic treatment is tobe prolonged for more than a fewweeks, topical BP should be added,or used in combination products.(SOR: C).

Oral Antibiotics

Interestingly, with the exception ofextended-release minocycline, use oforal antibiotics in acne is not FDA ap-proved.61 Extended-release minocy-cline dosed at 1 mg/kg per day

(administered as 1 tablet daily) is FDAapproved for the treatment of moder-ate to severe inflammatory acne vul-garis that is not predominantly nodularin patients $12 years of age.62 Bothimmediate-release doxycycline andimmediate-release minocycline havelisted the indication in their FDA-approved labeling of adjunctive usefor severe acne, although this was notbased on formal submission for FDAapproval for either drug.63,64 The com-monly used oral antibiotics for childrenolder than 8 years are tetracyclinederivatives, including tetracycline,doxycycline, and minocycline. Althougherythromycin was used successfully inthe past, the worldwide prevalence ofP acnes resistance to erythromycinhas led to decreased use of this agent,both orally and topically, for acne.60,65,66

Comparative studies are limited, butthe second-generation tetracyclines,doxycycline and minocycline, are pre-ferred because of pharmacokineticadvantages allowing for once-dailyadministration in most cases, greaterlipophilicity that is believed to augmentfollicular penetration, and lower prev-alence of resistant P acnes strains ascompared with tetracycline.15,67,68 Forchildren under 8 years of age andthose with tetracycline allergies, al-ternative oral antibiotic agents, in-cluding erythromycin, azithromycin,and trimethoprim/sulfamethoxazole,should be used very judiciously be-cause of the potential risk for severeadverse reactions, such as toxic epi-dermal necrolysi.69–72 Table 5 sum-marizes the dosages, adverse events,and precautions regarding the use ofthe most frequently used oral anti-biotics for treatment of inflammatoryacne.69

The panel agreed that education andmonitoring related to potential adverseevents is important with oral antibiotictherapy for acne. Photosensitivity (pho-totoxicity) and “pill esophagitis” are

most common with oral doxycycline.73–75

The former can be circumvented withappropriate photoprotection, and thelatter by ingestion with a large glassof water, maintaining an upright posi-tion for at least 1 hour after ingestion,and use of an enteric-coated formula-tion.76 Although rare, drug hypersensi-tivity syndrome (DHS), Stevens-Johnsonsyndrome, or lupuslike syndrome (LLS)may occur with administration ofminocycline. DHS presents early afterinitiation of minocycline therapy, usu-ally within the first 2 to 8 weeks,commonly with flulike symptoms (ie,fever, malaise), diffuse exanthemlikeerythema, facial edema, cervical lymph-adenopathy, and elevated hepatic en-zymes (especially transaminases),although other organs may be in-volved with interstitial inflammation(eg, pneumonitis, nephritis, and thy-roiditis).77,78

Minocycline-associated LLS, which iscommonly reversible, generally devel-ops after chronic exposure (ie, manymonths to years), and often presentswith malaise, distal polyarthralgiaswith orwithout polyarthritis, and,morerarely, autoimmune hepatitis.78–80 Mostcases of minocycline-associated LLS donot have skin eruptions, although rarereports have revealed superficial vas-culitis such as cutaneous polyarteritisnodosa. A positive antinuclear antibodytest is often present, although not alwaysdiagnostic or predictive of minocyclineLLS, along with other autoantibodies.The autoantibody profile may be highlyvariable among cases of minocycline-associated LLS. When present, p-ancapositivity is believed to strongly sup-port the diagnosis. Presence of antihi-stone antibody is not required toconfirm the diagnosis of LLS and maynot be detected in some cases. Finally,within the first few weeks of minocy-cline treatment, physicians should con-sider the rare risk of serumsicknesslikereaction.78 Cutaneous and/or mucosal




TABLE 5 Oral Antibiotics Used for Treatment of Moderate-to-Severe Acne Vulgaris

Antibiotic Recommended Dosage Potential Adverse Effects Comments

Doxycyclinea 50–100 mg QD or BID;150 mg QD

Gastrointestinal upset especially pillesophagitis (reduced with enteric coatedformulation); photosensitivity (especially indoses of $100 mg daily); staining offorming tooth enamel (if given#8 y of age);vaginal candidiasis; BIH (rare).

Can be taken with meals, take with large glassof water andmaintain upright position$1 hto decrease risk of esophagitis; optimizephotoprotection especially in sunny seasonor with known increased outdoor exposure;avoid in children who have not developedset of permanent teeth; monitor for blurredvision, severe headaches sometimes withnausea and/or vomiting.

Erythromycinb 250–500 mg QD-BID Gastrointestinal upset; drug-drug interactionssuch as increase in carbamazepine serumlevels → toxicity.

High prevalence of antibiotic-resistant Pacnes.

Tetracycline 500 mg BID Fixed drug eruption; gastrointestinalsymptoms; staining of forming tooth enamel(if given #8 y of age); vaginal candidiasis;BIH (rare).

Ingest on empty stomach preferable;absorption is decreased if taken with iron,calcium, or many other metal ions found invitamins/supplements, dairy products(including milk, yogurt); avoid in childrenwho have not developed set of permanentteeth; avoid in renal or hepatic disease;monitor for blurred vision, severeheadaches sometimes with nausea and/orvomiting.

Minocycline (immediate release) 50–100 mg QD-BID Cutaneousand/ormucosal hyperpigmentationof skin and mucosal sites (oral, sclera,conjunctiva); bone may be affected in somecases; DHS (systemic) often with hepatitisand/or pneumonitis (most often will occurwithin the first 1–2 mo); hepatitis(hypersensitivity [tends to occur moreacutely early in treatment course] orautoimmune [more often to occur withmore chronic use of several months toyears]); LLS; Stephens-Johnson syndrome;vestibular toxicity (tends to occur within thefirst few days after starting therapy);staining of forming tooth enamel (if given#8 y of age); vaginal candidiasis; BIH (rare).

Can be taken with meals; warn patient aboutdizziness/vertigo (suggest initial doses begiven when at home and not driving toassess if patient susceptible to theseeffects); avoid in children who have notdeveloped set of permanent teeth; monitorfor malaise, flulike symptoms, diffuseerythema with facial swelling, respiratorycomplaints suggestive of drughypersensitivity especially within the firstfew months after starting therapy;discontinue therapy if this side effectsuspected; monitor for malaise, distalarthralgias with or without arthritisespecially with more prolonged use ofseveral months to years suggestive of LLS;monitor for pigmentary changes on skinespecially face, trunk, legs, and scars;monitor for blue or gray discoloration ofsclera, oral mucosa, nail beds; monitor forbluediscolorationofacnescars; somecasesmaybepersistentevenwithdiscontinuation;monitor for blurred vision, severeheadaches sometimes with nausea and/orvomiting.

Minocycline extended-release tablets(available since 2006)

1 mg/kg QD Same potential reactions as above althoughabove side effects reported predominantlywith immediate-release formulations(available since 1971); lower incidence ofacute vestibular side effects with weight-based dosing (1 mg/kg per day).

Same as above except lower incidence of acutevestibular side effects with weight-baseddosing (1 mg/kg per day); not yet known ifother potential side effects reduced withweight-based dosing of the extended-release formulation; less accumulation ofminocycline over time due topharmacokinetic properties of extended-release formulation; may possibly correlatewith decreased risk of cutaneous ormucosal hyperpigmentation if dosedproperly by patient weight.

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hyperpigmentation may occur in somepatients treated with minocycline andappears to correlate with cumulativedrug exposure over time in mostcases reported with use of immediate-release minocycline formulations av-ailable since 1971.81–83 Weight-baseddosing of minocycline (1 mg/kg perday) using the extended-release tabletformulation once daily, available sincemid-2006, may potentially reduce therisk of hyperpigmentation as both thepeak serum level and total drug ex-posure are diminished as comparedwith immediate-release minocyclineformulations; however, continued phar-macosurveillance is warranted to con-firm this preliminary observation.84

Face, trunk, legs, oral mucosa, sclera,and nail beds should be examined pe-riodically.

Acute vestibular adverse events (ie,vertigo, dizziness) that sometimesoccur in patients treated with mino-cycline develop early after initiation oftreatment and are reversible withdiscontinuation of therapy.85–87 Weight-based dosing of extended release-minocycline (1 mg/kg once daily) hasbeen reported to reduce the risk fordevelopment of acute vestibular ad-verse events as compared with a dailydose up to threefold higher.61

A rare central nervous system-relatedside effect associated with use of tet-racycline, doxycycline, orminocycline isbenign intracranial hypertension (BIH),

also referred toaspseudotumorcerebri.A high index of suspicion is warrantedif headache and visual disturbances,sometimes accompanied by nauseaand/or vomiting, are noted to detect BIHearly because persistence can lead tosevere loss of vision, which may bepermanent.88

In the past 20 years, P acnes has be-come less sensitive to oral and topi-cal antibiotics because of increasingselection pressure arising from theirwidespread usage.60,66,70,89 However,strategies listed in Table 6 can mini-mize the potential for the de-velopment of resistance to antibioticswhen used to treat acne, especially asthe duration of therapy is often pro-longed over months. Recent studieshave revealed that the use of sys-temic antibiotics for acne treatmentalso may be associated with an in-crease in resistant coagulase-negativestaphylococci and a possible in-creased risk of upper respiratorytract infection; however, furtherstudies are needed to evaluate thetrue clinical implications of these po-tential risks.60,90


� Oral antibiotics are appropriatefor moderate-to-severe inflamma-tory acne vulgaris at any age. Tet-racycline derivatives (tetracycline,doxycycline, and minocycline) shouldnot be used in children younger than8 years of age. (SOR: B).

� Second-generation tetracyclines(doxycycline, minocycline) are some-times preferred to tetracycline be-cause of ease of use, fewer problemswith absorption with food and min-erals in vitamins and other supple-ments, and less-frequent dosing.(SOR: C).

� Patients should be educated andmonitored for potential adverseevents when utilizing oral antibiot-ics for acne. (SOR: B).

Topical Dapsone

Dapsone, a synthetic sulfone, has anti-microbial and antiinflammatory effects;however, its activity in the treatment

TABLE 5 Continued

Antibiotic Recommended Dosage Potential Adverse Effects Comments

Trimethoprim/ sulfamethoxazole 160–800 mg BID Severe cutaneous eruptions (toxic epidermalnecrolysis, Stevens-Johnson syndrome);bone marrow suppression (anemias,neutropenia, and thrombocytopenia);hypersensitivity reactions; drug eruptions(rash); fixed drug eruption.

Not generally recommended for use as first orsecond-line agent for acne; to be usedjudiciously in selected refractory cases;obtain complete blood cell count at baselineand periodically thereafter; additionalcaution in patients with history of anemia(megaloblastic types); may warranthematologic consultation if use of this agenthighly considered.

BID, twice daily; QD, once daily. Adapted from Tan,69 Gollnick et al,15 and Del Rosso and Kim.70a Enteric-coated and double-scored 150 mg tablet available; double-scored tablet provides 50 mg/unit (tablet can be administered whole or broken into total of 3 segments).b Use of lower dose for maintenance therapy based on anecdotal experience or clinical impression and not by large-scale clinical trials.

TABLE 6 Strategies to Optimize OralAntibiotic Therapy in Acne Vulgaris

Use in moderate or severe inflammatory acnevulgaris in combination with a topical regimenthat includes BP.

Avoid antibiotic monotherapy when using either anoral or topical antibiotic agent for acne vulgaris.

Discontinue (or taper) within 1 to 2 mo once newinflammatory acne lesions have stoppedemerging.

Incorporate a topical retinoid into the regimenearly to augment overall therapeutic benefit andprepare for discontinuation of oral agent withgoal of maintaining control with topicalprogram; may also use BP-containingformulation with topical retinoid formaintenance of control of acne.

If retreatment is needed, use the same oralantibiotic that was previously effective in thepast.

Adapted from Gollnick et al,15 Leyden,50 and Del Rosso andKim.70




of acneas a topical agent is not believedto be related to P acnes reduction.91

Recently, a 5% dapsone gel was ap-proved in the United States for acnetreatment. It was evaluated in two 12-week randomized, double-blind, phase3 trials in patients aged 12 and olderwith mild, moderate, or severe acne.92

The 3010 subjects used dapsone 5%gel twice daily or vehicle gel. A com-bined analysis revealed a statisticallysignificant reduction in noninflam-matory and inflammatory lesions byweek 12 compared with vehicle (P ,.001). Treatment response was rapid,with statistically significant inter-group differences in lesion count at4 weeks. Adverse events were com-parable between dapsone gel andvehicle gel and rarely led to discon-tinuation.

Available studies demonstrate thattopical dapsone is most effectiveagainst inflammatory lesions, with ef-ficacy enhanced more when combinedwith a topical retinoid as comparedwith BP.92,93 The safety of 5% dapsonegel applied twice daily has been dem-onstrated in patients who are glucose6 phosphate dehydrogenase-deficientand in patients who are sulfonamideallergic.94–96 Themost commonapplication-site reactions consisted of erythemaand dryness that were similar be-tween groups. A temporary orangestaining of the skin can occur whenBP and topical dapsone are usedtogether.

Oral Isotretinoin in Severe Acne

Oral isotretinoin targets all of thepathophysiologic factors involved inacne typically producing excellentresults.15 A recent consensus con-ference on its use recommendsa starting dose of 0.5 mg/kg per dayfor the first 4 weeks to avoid initialflares, increasing to the full dosage of1 mg/kg per day.97 The panel concurswith this recommendation for iso-

tretinoin use in acne treatment ofadolescents and preadolescents andagrees that it may be used in youngerpatients with severe, refractory, andscarring acne.

Its most common side effects includedry, chappedskin and lips, dry eyes, andmyalgias. Nose bleeds secondary todrynessalsoarecommon. Theseeffectsare generally reversible upon discon-tinuation of the drug. Some patientsmay experience increases in serumtriglycerides and changes in liverenzymes. Both fasting serum lipids andliver function tests should be obtainedat baseline and monitored periodicallythereafter. A major adverse effect ofisotretinoinandapublichealthconcernis its teratogenic potential. For thisreason, the FDA mandated in 2007 theimplementation of a computerized riskmanagement program (iPledge), whichregisters all isotretinoin patients, phy-sicians, pharmacies, and manufac-turers andensuresmonthlymonitoringof pregnancy status in females ofchildbearing potential.

Three of the most significant and con-troversial groups of adverse effectsattributed to isotretinoin and de-scribed in the drug’s package insertare skeletal issues; potential for de-velopment of inflammatory boweldisease (IBD); and mood changes, de-pression, suicidal ideation, and sui-cide, which are addressed in greaterdetail because of their relevance inpediatric patients.98

Bone Effects

The interaction between retinoids andskeletal homeostasis is complex. Ani-mal studies have indicated that exces-sive intake of retinoids can haveinhibitory effects on both osteoblastand osteoclast activity that may posea theoretical risk for fractures or hy-perostosis.99–112 Well-designed clinicalstudies involving human subjects havegenerated conflicting data on the as-

sociation between excessive intake ofvitamin A with the incidence of frac-tures. In evaluating isotretinoin spe-cifically, 1 small prospective cohortstudy associated isotretinoin withminimal-to-mild bone demineralizationat specific sites (such as Ward’s tri-angle of the femur), but revealed thatthese effects may be reversible.113 Ad-ditional data from small prospectivecohort114 and case control studies115,116

have, however, documented no mea-surable changes in bone mineralizationmarkers. These changes were not as-sociated with increased risk of frac-tures in those treated with isotretinoinat the standard doses and durationsused for acne.

Hyperostoses are thought to occur withsomewhat greater frequency amongthose who received long-term systemicretinoid therapy for disorders of kera-tinization. Hyperostosis during retinoiduse has been most strongly associatedwith long-term therapy or chemo-prevention, appears to be dose- andduration-dependent, is often asymp-tomatic, and may resolve spontane-ously. Overall, this phenomenonappears to be uncommon among thosereceiving isotretinoin for acne vulgaris.

Premature epiphyseal closure in as-sociationwith retinoid therapy appearsto be a rare event and may occur in anasymmetric or generalized fashion.Only a single case has been reported inassociation with isotretinoin adminis-tered for acne.117 Other cases haveprimarily been reported as a conse-quence of isotretinoin therapy fordisorders of keratinization118 or neu-roblastoma.113,119

IBD

There are conflicting data on the po-tential associationbetween isotretinoinand IBD. In available published reports,21 patients with preexisting IBD whosubsequently receive isotretinoin havebeen reported to tolerate the drug;

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4 experienced worsening of IBD symp-toms during therapy, suggesting thatthe majority of patients with IBD whoreceived isotretinoin have largely tol-erated isotretinoin for acne.107,120–128

The occurrence of IBD after exposure toisotretinoin has been reported. Theseare composed of case reports or smallcase series (N = 18); a systematic re-view of FDA MedWatch Data129 high-lighting 85 identified cases, of which 62were deemed highly probable orprobable; and 1 large case-controlstudy involving 8189 cases of IBD,which included 24 cases that had re-ceived isotretinoin.130 In this case-control study, only ulcerative colitiswas associated with previous iso-tretinoin use, and increasing cumula-tive dose or duration to isotretinoinwas associated with an elevated risk ofulcerative colitis (1.5 odds ratio in-crease per 20 mg increase in dose, and5.63 overall increased odds ratio inassociation with longer duration).

At the same time, a case-control studyevaluatingaManitoba IBDEpidemiologyDatabase revealed no evidence for anassociation between IBD and iso-tretinoin use131; in addition, a system-atic literature-based search of casereports, case series, and clinical trialslikewise revealed no evidence for anassociation.132

An association between IBD (in partic-ular, ulcerative colitis) and isotretinoin,therefore, may potentially exist, al-though if it does, it appears to affecta small subset of patients. The phe-nomenon appears to be rare, seems tobe idiosyncratic, and, at present, thereare no identifiable clinical character-istics that can currently a priori predictthis type of response. The association isalso fraught with confounding factors,since the highest age of IBD onsetoverlaps the agewhen patients developsevere acne and when isotretinoin istypically used. In addition, it was noted ina study by Margolis et al114 that the ma-

jority of patients prescribed isotretinointreatment have been on extended an-tibiotic therapy and that previous an-tibiotic use may be an importantconfounding variable in the relation-ship between IBD and isotretinoin.Furthermore, a potential link betweenIBD and inflammatory acne itself can-not be excluded.

Mood Disorders

The evidence regarding an associationbetween isotretinoin use and mooddisorders is primarily anecdotal, withthe original case series of 24 patientsreported by Hazen comprising thereported experience on this linkage.One open-label study compared acnepatients recalcitrant to antibiotics tothose receiving isotretinoin, and iden-tified changes in brain metabolism inthe orbitofrontal cortex, which arethought to partiallymediate depressivesymptoms.133 However, the numbers ofpatients studied were small (N = 28),and those receiving isotretinoin hadmore severe acne, which could corre-late with more severe depressivesymptoms independent of the iso-tretinoin. Indeed, in a large cross-sectional questionnaire-based studyof 3775 adolescents between 18 and 19years of age who suffered from acne,those with more severe acne weremore than twice as likely to havemental health issues and 1.8 timesmore likely to have suicidal ideation. Infact, ∼1 in 4 adolescents with signifi-cant acne were noted to have mentalhealth issues. A systematic review byMarqueling and Zane134 identified 6prospective studies and 3 retrospec-tive studies that involved at least 20patients, studied depressive symptomsin human subjects as primary data,and used epidemiologic techniques. Inthis analysis, there was no apparentincrease in depression diagnoses orsymptoms when baseline was com-pared with after treatment with iso-tretinoin. Four subsequent additional

studies (2 prospective, 1 case-control,and 1 cohort study) evaluated iso-tretinoin use and depressive symp-toms.135,136 Although none of theseadditional studies identified a positiveassociation between isotretinoin useand depression, 2 of them indicatedthat as acne improved, quality of lifeimproved137 and depressive symp-toms and suicidal ideation actuallydecreased.138

In summary, case reports and caseseries have identified patients whodeveloped depressive symptoms whilereceiving or after isotretinoin therapy,and 1 study utilizing positron emissiontomography has documented changesin cerebral metabolism in patients re-ceiving isotretinoin therapy. Epidemio-logic studies, however, do not currentlysupport a causative association be-tween isotretinoin and depression, andacne severity itself is a predictor ofmental health issues and suicidal ide-ation. Ongoing vigilance and surveil-lance of patients for mood changeswhile on isotretinoin therapy seemreasonable, but the data appear reas-suring.


� Isotretinoin is recommended forsevere, scarring, and/or refractoryacne in adolescents and may beused in younger patients. (SORadolescents: A; SOR preadolescentsand younger: C). Extensive counsel-ing, particularly regarding theavoidance of pregnancy as wellas careful monitoring of potentialside effects and toxicities, is rec-ommended.

PRESCRIPTION TREATMENTOPTIONS: TOPICAL FIXED-DOSECOMBINATION THERAPIES

Numerous topical fixed-dose combina-tion products, including BP/clindamycin,BP/adapalene, BP/erythromycin, andtretinoin/clindamycin, are currently FDAapproved for pediatric patients 12 years




and older as outlined in Table 7. All of theproducts are pregnancy category C.

In the phase 3 pivotal trials for BP 2.5%/clindamycin 1.2% gel (Acanya, CoriaLaboratories), 62% of enrolled patientswere between the ages of 12 and 17. Ina subanalysis of 12- to 17-year-oldpatients, lesion count and successrate were similar to those obtained inthe study as a whole.139 In the pivotaltrial for tretinoin 0.025%/clindamycin1.2% (Ziana Gel, Medicis Pharmaceuti-cal Corporation, Scottsdale, AZ), 51% ofenrolled patients were 12 to 17 years ofage and, in an unpublished subanalysisfor the pediatric age group, was es-sentially no different from the studygroup as a whole. In the BP 2.5%/adapalene 0.1% gel (Epiduo Gel,Galderma Laboratories, LP, Fort Worth,TX) pivotal trial, the mean age was 16.2years and a subanalysis of results inthe 12- to 17-year-old group was simi-lar to the study group as a whole.140

Although sometimes more costly thansingle agents prescribed separately,fixed combinations applied once dailyare very convenient and thus may im-prove adherence.52,141


� Fixed-dose combination topical ther-apies may be useful in regimens ofcare for all types and severities ofacne. (SOR adolescents: A; preado-lescents and younger: B).

HORMONAL THERAPY

Hormonal therapy in acne is directed atsuppressing ovarian androgen pro-

duction and blocking the effects ofandrogens on the sebaceous gland thatleads to reduction of sebumproductionand improvement in acne. Combinationoral contraceptives (OCs; estrogen plusprogestin)block theovarianproductionof androgen, and antiandrogens, suchas spironolactone, block the effects ofandrogens on the sebaceous gland. Inpatients diagnosed with congenitaladrenal hyperplasia, low-dose gluco-corticoids are used to suppress theadrenal production of androgens.

Although others have antiacne efficacy,only 3 combinationOCsare currently FDAapproved for the treatment of acne(Ortho Tri Cyclen [norgestimate/ethinylestradiol] Tablets indicated for use inmoderate acne in females $15 yearsof age; Estrostep [norethindrone acetateand ethinyl estradiol] Tablets indi-cated for use in moderate acne forfemales $15 years of age; and Yaz[drospirenone/ethinyl estradiol] Tabletsfor moderate acne in females$14 yearsof age). The reduction in the estrogendosage of OCs has lowered the risk ofthromboembolism associatedwith someof the earlier OC formulations, althoughthis relationship is still under review bythe FDA. Although absolute thromboem-bolic risk is low in adolescence, it isrecommended that a family history ofthrombotic events be obtained andyoung patients are asked if they smokebefore OCs are prescribed. The mostcommon adverse events related to theiruse include nausea/vomiting, breasttenderness, headache, weight gain, andbreakthrough bleeding.

The most important issues regardingthe use of combination OCs in the pe-diatric population involve whether lowdoses of estrogen provide sufficientestrogen for bone accrual and at whatage it is safe to initiate use. Approxi-mately 50% of bone mass is accruedbetween the ages of 12 and 18 years.142

Some experts believe that it is impor-tant to allow the development of asmuch bone mineral density (BMD) aspossible before initiating treatmentwith exogenous estrogen.

In a 24-month study of postmenarchalgirls with a mean age of 16.0 6 1.4years who were treated with an OCcontaining 100 mcg levonorgestrel and20 mcg ethinyl estradiol, there wasa mean increase in lumbar spine BMDat the femoral neck in 4.2% of girls whoreceived OC versus 6.3% in untreatedcontrols.143 The use of OCs did not re-sult in osteopenia in any subject. Nev-ertheless, the authors concluded that itis unclear whether the currentlyavailable low-dose OC containing 20mcg ethinyl estradiol is adequate forbone mass accrual in this age group. Along-term study of combined OCs withcalcium supplementation revealed noeffect on BMD after 10 years.144 Re-ferral to an adolescent medicine spe-cialist or gynecologist for managementof OC treatment remains dependent onthe physician’s comfort level.

Spironolactone is a synthetic steroidalandrogen receptor blocker that is oftenused in female acne patients.145,146 Inselect groups of acne patients, spi-ronolactone has revealed efficacy,147–149

although its overall role in acne therapyand appropriate age to initiate treat-ment has not yet been fully deter-mined.150 There are minimal data on itsuse in pediatric acne.


� Hormonal therapy with combinedOC may be useful as second-linetherapy in regimens of care in pu-bertal females with moderate-to-

TABLE 7 Topical Fixed-Dose Combination Prescription Acne Therapies

Product Active Ingredients and Concentration

Acanya Gel Clindamycin phosphate, 1.2%; BP, 2.5% (aqueous-based)BenzaClin Gel (generic available) Clindamycin phosphate, 1%; BP, 5% (aqueous-based)Benzamycin Gel (generic available) Erythromycin, 3%; BP, 5% (alcohol-based)Duac Gela Clindamycin phosphate, 1%; BP, 5% (aqueous-based)Epiduo Gel Adapalene, 0.1%; BP, 2.5%Veltin Gel Clindamycin phosphate, 1.2%; Tretinoin, 0.025%Ziana Gel Clindamycin phosphate, 1.2%; Tretinoin, 0.025%a Duac Gel is indicated for inflammatory acne vulgaris.

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severe acne. Tobacco use and familyhistory of thrombotic events should

be assessed. (SOR adolescents: A).

� Because of concerns about growthand bone density, many expertsrecommend withholding OC for

acne unassociated with endocrino-logic pathology until 1 year after

onset of menstruation. (SOR: C).

FIGURE 1Pediatric treatment recommendations for mild acne.




FIGURE 2Pediatric treatment recommendations for moderate acne.

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FIGURE 3Pediatric treatment recommendations for severe acne.




EVIDENCE-BASED TREATMENTRECOMMENDATIONS FORPEDIATRIC ACNE

When selecting acne treatment, it isimportant to assess severity as a func-tion of number, type, and severity oflesions as well as psychological impacton thepatient including the likelihoodofscarring and/or dyspigmentation. Thepanel recommendspediatric treatmentrecommendations based on severity ofmild, moderate, and severe acne asdiscussed later.

Mild Acne

Mild acne may present as pre-dominantly comedonal or as mixedcomedonal and inflammatory disease(Fig 1). Evidence-based treatment rec-ommendations by the panel for mildacne are highlighted in Fig 1.

Initial Treatment

Topical therapy alone or in combinationis recommended as initial treatment ofmild acne. BP as a single agent, topicalretinoids, or combinations of topicalretinoids, antibiotics, and BP as in-dividual agents or fixed-dose combi-nations may be used.

In patients of color in whom the pro-pensity for scarring and PIH is greater,initial treatment also might include anoral or topical antibiotic.151 Dependingon patient and parent preference,treatment could be initiated withmonotherapy, including OTC products.OTC products are generally effective forvery mild acne, but, with the exceptionof BP, data on the efficacy of theiringredients are lacking. Patientsshould be counseled that it takes∼4 to8 weeks to demonstrate visible resultsfrom any acne treatment.


� Initial therapy for mild acne mayinclude OTC products such as BPas a single agent, topical retinoids,or combinations of topical retinoids,

antibiotics, and BP as individualagents or fixed-dose combinations.(SOR adolescents: A; SOR preado-lescents and younger: B).

Inadequate Response

If response to first-line treatment isinadequate, it is important to checkadherence by asking the patient and/ortheparent and, if necessary, to reiterateusage instructions. If adherence ap-pears to be adequate, a topical retinoidor BP may be added to monotherapywith either agent. It has been shownthat early initiation of clindamycin/BP +adapalene produced earlierand greaterreductions in lesion counts when com-pared with adapalene monotherapy orBP/clindamycin for 4 weeks, with ada-palene added at week 4.152 The con-centration, type, and/or formulationof the topical retinoid may be changed,or the topical combination therapycan be changed. Another option toconsider is topical dapsone; however,the panel notes large-scale compara-tive studies of dapsone versus othertopicals are lacking, particularly in pe-diatric patients.

Moderate Acne

Although it is recommended to startwith the least aggressive, effectiveregimen, moderate (Fig 2) and severeacne typically requires a more ag-gressive regimen, possibly with theaddition of oral antibiotics (Fig 3).

Initial Therapy

Initial therapy for moderate acne mayinclude topical combination therapiesas described earlier or with combina-tions that include topical dapsone.

Adding an Oral Antibiotic

Overall, oral antibiotic therapy is a safeand effective approach to the treatmentof moderate-to-severe inflammatory ormixed comedonal and inflammatoryacne vulgaris used for more than 5

decades.Physiciansmayelect to initiatetreatment of moderate acne witha topical regimen and add an oral an-tibiotic if the therapeutic response isnot adequate. Alternatively, an oralantibioticmaybestartedconcomitantlywith a topical regimen for moderate-to-severe acne. Optimally, the topicalregimen would include a retinoid anda BP-containing formulation, eitherseparately orasacombinationproduct.In addition, use of an oral antibioticmaybe especially prudent if there is evi-dence of acne scarring, even if thecurrent severity of inflammatory acneis more modest.151 Importantly, someoral antibiotics, especially tetracyclinederivatives, in addition to antibioticactivity against P acnes, exhibit certainantiinflammatory and immunomodu-latory properties that may be operativein counteracting mechanisms or path-ways involved in acne lesion de-velopment.60,153–155

Typically, 4 to 8 weeks of compliant oralantibiotic use are needed before theclinical effects of an oral antibiotic arevisible,whereasmaximal responsemayrequire 3 to 6 months of administra-tion.15,70 Once the formation of new in-flammatory lesions, defined as lesionsthat are raised by palpation, aremarkedly diminished in number, con-sideration may be given to stoppingoral antibiotics with continuation oftopical therapy to maintain control ofacne.


� Moderate acne may be initiallytreated with topical combinationsincluding a retinoid and BP and/or antibiotics, or with oral antibiot-ics in addition to a topical retinoidand BP and/or topical antibiotics.(SOR adolescents: A; SOR preado-lescents and younger: C).

Inadequate Response

If response to the above topical com-bination regimens with or without oral

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antibiotics is inadequate, adherenceshould again be evaluated. Referral toa dermatologist or pediatric derma-tologist may be considered if responsehas been poor and there is continuedpatient or parental frustration. Thetype, strength, or formulation of theretinoid, BP, or BP-antibiotic componentof the topical regimen may be changedto increase potency or adjusted to re-duce skin irritation if present or tosimplify the steps of application.

Severe Acne

Patients with severe acne are at sig-nificant risk for scarring (Fig 3). Thepanel recommends that the promptinitiation of appropriate treatment isessential to control the condition andprevent permanent skin changes.

Initial Treatment

Although the therapeutic agents are thesameas thoseused inmoderate acne, itis recommended that an oral antibioticshould be part of the initial treatmentand should be usedwith eithera topicalretinoid + BP with or without topicalantibiotics.


� Severe acne should be treated withoral antibiotics and topical reti-noids with BP, with or without top-ical antibiotics, with considerationof hormonal therapy in pubertalfemales, oral isotretinoin, and der-matology referral. (SOR: C).

Inadequate Response

In cases of inadequate response,compliance with the prescribed regi-men should be reassessed first. If ad-herence has been adequate, the oralantibiotic agent or class may bechanged. For instance, if doxycyclinehas provided only a partial response,minocycline might prove a more ef-fective alternative. For female patients,combination OC therapy should be

considered. Both male and femalepatients unresponsive to these topicaland oral therapies will benefit fromconsideration of oral isotretinoin.

RECOMMENDATIONS FOR ACNEMANAGEMENT IN THEPREADOLESCENT

The algorithm for acne management ofthe preadolescent is essentially thesame as for the adolescent, thoughthese recommendations are basedmore strongly on expert opinion. Anti-biotics in the tetracycline class shouldnot be used for the treatment of acne inpatients under 8 years of age.

OTHER CONSIDERATIONS FORPEDIATRIC ACNE TREATMENTSELECTION

A number of additional considerationsare pertinent to acne managementand selection of therapies in pediatricpatients. Chief among them are anunderstanding of previous treatmenthistory, cost ofmedications, ease of useand regimen complexity and its impacton adherence, vehicle selection, activescarring, and psychosocial impact ofthe acne on the individual. In addition,the influence of diet on acne, an area ofevolving understanding, may be con-sidered.

Previous Treatment and History

At the initial assessment, it is crucial toinquire about previous treatment his-tory, if any. An important question iswhether the patient responded toa specificfirst-line regimen. If so, unlessthere are circumstances dictatingotherwise, treatment should be reini-tiated with the previous regimen orsome of its elements. However, if re-sponse to previous therapies has beenpoor, up-titration, add-on therapies, orswitching to an alternative should beconsidered.156

Financial Costs

In addition to the aforementionedconsiderations, patient resources andthefinancial costs of treatmentmust beconsidered when selecting a treatmentregimen from the panel recommen-dations. A recent retrospective cross-sectional study by Patel et al157 of 3784 816 patients with acne and similarconditions indicated there was a sig-nificant overall decrease in reportedtotal annual prescription spendingwidely attributed to the reduction oforal antibiotic use and increase in theuse of OCs and oral retinoids. Further,the use of topical retinoids was pre-ferred in combination with other treat-ments rather than as monotherapy.Managed-care organizations are in-creasingly requiring cost-sharing, andit may be necessary to adapt prescrib-ing preferences to patient resources.

Ease of Use, Regimen Complexity,and Adherence

Adherence is the contemporary termi-nology for persistence in use of a rec-ommended medical treatment anddenotes a partnership between thepatient and the physician. Adherencewithanacnetreatmentregimen isasinequa non of successful management. Infact, lackofadherence isamajor reasonfor acne treatment failures.158 Preven-tion and proactive education is easierthan dealing with nonadherence aftertreatment response has been inade-quate.5 Therefore, adherence to theprescribed regimen should be asses-sed at each visit, particularly if theresponse is less than expected. Adher-ence is a function of cost ofmedications/therapies, ease of use/regimen simpli-city, patient preferences, tolerability,rapidity of results, and patient or par-ent understanding.

Vehicle Selection

In 1 small study, it was found thatnonadherencewithacne treatmentwas




52% after 3 months.159 Adherence maybe improved through patient and parenteducation, selection of a simple regi-men, more frequent doctor visits, andchoice of vehicles that improve medica-tion tolerability. One study revealed a di-rect correlation between adherence anddosing frequency, with 83.6% of patientscomplying with once-daily dosing versus74.9% with twice-daily dosing. Fixedcombinations of topical medicationsmay be helpful in this regard.

Empowering patients with control overtheir care is important for adher-ence.160 It is essential to elicit informa-tion at each doctor visit about patientpreferences and lifestyle. For example,a water-based gel may be the optimalchoice for the patient who wearsmakeup.161 Teenagers, especiallymales,may not like the feel of moisturizers butmay accept a gel, pad or foam, or in-shower wash.160 Other vehicle consid-erations center around tolerability,which is influenced by the medication’simpact on the skin barrier. Many topicalmedications are being formulated invehicles, including aqueous gels, whichare therapeutic andmay help rehydrateand repair the skin barrier.161 It may beuseful to initiate treatment with ex-tremely mild topical agents until theskin has adjusted to medication effectsand patients have adapted to sideeffects.160

Active Scarring

The likelihood of scarring is an im-portant consideration in treatmentselection. Patients with moderate andsevere acne are at increased risk ofscarring, as are thosewithmore deeplypigmented skin.151 Hence, aggressivetreatment is warranted to preventpermanent sequelae in these patientpopulations.

Psychosocial Impact

The psychosocial impact of acne is in-fluencedbynumerous factors including

age, diseaseseverity, social and familialnetworks, and individual personalities.Adolescents with substantial acne arereported to have high rates of mentalhealth problems, affective isolation,social impairment, depression, andsuicidal ideation.162 In the cases wherethe impact on the psychosocial healthof the patient is particularly burden-some, effective treatment of acne mayresult in improvements in self-esteem,affect, shame, embarrassment, bodyimage, social assertiveness, and self-confidence.150

Managing Expectations

Adolescents are notoriously impatient.Physicians, who see the patient atintervals rather than daily, may noteimprovement between visits that maynot be readily apparent to the adoles-centwhoexamineshis or her face in themirror several times per day.156 A basicunderstanding of acne pathophysiol-ogy and how prescribed agents workto control acne may augment adher-ence.163 For example, both patients andparents should be given reasonableexpectations of the time to visible im-provement. It is important to explainthat acne may worsen or irritation maybemore significant initially, with gradualimprovement. An understanding of the“invisible microcomedo” helps patientsunderstand why topical medicationsshould be applied to the entire face.

Many adolescents believe that acne isrelated to facial hygiene, and so theymay try treating themselves with harshastringents, abrasives, or vigorousscrubbing. It is important for them tounderstand that such treatment mayactuallyworsen theiracneand increasethe likelihood of inflammation andscarring. Many clinicians prefer to rec-ommend an appropriate gentle, dailyskin-care regimen, including a non-comedogenic moisturizer and sun-screen for the patient to use with theprescribed treatment(s).

Diet and Acne

Consideration of a role for diet in con-tributing to acnearose in the 1930s, andchocolate, sugar, and iodine wereamong the dietary factors implicated.As a result of a series of studies in thelate1960s that failed to identifyadietaryconnection, the concept fell out offashion.164 However, the debate hasbeen rekindled in response to a varietyof data emerging over the last decade.

A retrospective recall-based study inadult nurses165 and a prospective self-assessment study in teenage girls166

both suggested an association be-tween acne and intake of milk andother dairy products. A subsequentprospective study in teenage boyssuggested an association with skimmilk,167 although the previous 2 studiesdid not identify a difference based onmilk fat content.

The effects on acne of glycemic load inthe diet also have been subjected toexamination. An anthropologic study168

comparing acne rates in a hunter-gatherer population in Papua NewGuinea versus those in the developedworld suggested that dietary glycemicload may contribute to the observeddifferences in acne incidence. A num-ber of prospective trials169,170 sub-sequently have been performed,notably including a randomized pro-spective controlled trial of a low gly-cemic diet versus a high glycemic dietin teenage boys.171 By the end of the12-week study, the low glycemic dietwas shown to provide superior reduc-tion in the number of total acne lesions(223.56 3.9 vs 212.0 6 3.5, P = .03),as well as reductions in inflammatorylesion count and other parameters in-cluding weight and BMI.

Other dietary constituents that are thesubject of renewed interest include zincand antioxidants; the role of chocolateis being reinvestigated in a blindedplacebo-controlled clinical trial (clin-icaltrials.gov). Based on the currently

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available data, it is difficult to point withcertainty to any dietary manipulationthat should be recommended to pedi-atric patients suffering from acne;however, consideration may be given inindividual cases to institution of a lowglycemic diet. Patient and parent edu-cation to dispel acne myths is an im-portant treatment consideration.

CONCLUSIONS

As the pathogenesis of acne vulgarisappears to be similar at all ages, the

sameprinciplesand therapeuticagentsapply to all age groups diagnosed withacne. However, age group differencesmay require special considerations inthe use of these agents, particularlywith regard to ease of use and patientadherence, cost factors, differences inpsychosocial impacts among agegroups, the likelihood of scarring, andthe use of advanced vehicles to mini-mize adverse effects on young skin.

Although there are many acne treat-ment approaches to consider, these

evidence-based treatment recommen-dations from the pediatric perspectivemay provide useful guidance in themanagement of acne vulgaris duringchildhood and adolescence. In mostcases, acne can be successfully treatedby nondermatologists. In other instan-ces, clinicians may decide that, in ad-dition to using these recommendations,consultation with another specialistsuch as a pediatric dermatologist orpediatric endocrinologist is appropri-ate.

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(Continued from first page)

ABBREVIATIONSAARS—American Acne and Rosacea SocietyBIH—benign intracranial hypertensionBMD—bone mineral densityBP—benzoyl peroxideDHS—drug hypersensitivity syndromeFDA—Food and Drug AdministrationIBD—inflammatory bowel diseaseLLS—lupuslike syndromeNCP—neonatal cephalic pustulosisOC—oral contraceptiveOTC—over-the-counterPCOS—polycystic ovary syndromePIH—postinflammatory hyperpigmentationSOR—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: [email protected]

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 Academyof Pediatrics (AAP). They received compensation from the AARS for participation in this consensus conference. Their participation included preparatoryconference calls, planning communications, extensive literature search and research on subject, preparation of presentations including slides, and manuscriptdevelopment, writing, and editing. No corporate benefactor of the AARS or AAP had any input into content preparation, data review, or any involvement in theoutcome 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 benefactorsinclude Galderma Laboratories, Medicis Pharmaceuticals, Ortho Dermatologics, and Valeant Pharmaceuticals. No corporate benefactor of the AARS or AAP had anyinput into content preparation or data review, or any involvement in the outcome of the meeting or publication.



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DOI: 10.1542/peds.2013-0490B2013;131;S163Pediatrics

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Zaenglein and Diane M. ThiboutotMancini, Seth J. Orlow, Albert C. Yan, Keith K. Vaux, Guy Webster, Andrea L.Hilary Baldwin, Sheila Fallon Friedlander, Moise Levy, Anne Lucky, Anthony J.

Lawrence F. Eichenfield, Andrew C. Krakowski, Caroline Piggott, James Del Rosso,Acne

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