Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric Acne abstract

26 Pages·2013·1.74 MB·English

SUPPLEMENTARTICLE
Evidence-Based Recommendations for the Diagnosis
and Treatment of Pediatric Acne
AUTHORS: LawrenceF.Eichenfield,MD,aAndrewC. abstract
Krakowski,MD,aCarolinePiggott, MD,aJamesDelRosso,
DO,bHilaryBaldwin,MD,cSheilaFallonFriedlander,MD,a
INTRODUCTION: Acne vulgaris is one of the most common skin con-
MoiseLevy,MD,dAnneLucky,MD,eAnthonyJ.Mancini,MD,f
ditions in children and adolescents. The presentation, differential di-
SethJ.Orlow,MD,PhD,gAlbertC.Yan,MD,hKeithK.Vaux,
MD,iGuyWebster,MD,PhD,jAndreaL.Zaenglein,MD,k,land agnosis, and association of acne with systemic pathology differs by
DianeM.Thiboutot,MDl age of presentation. Current acknowledged guidelines for the diag-
aDivisionofPediatricandAdolescentDermatology,Rady nosis and management of pediatric acne are lacking, and there are
Children’sHospital,SanDiegoandDepartmentsofPediatricsand variations in management across the spectrum of primary and spe-
Medicine(Dermatology),UniversityofCalifornia,SanDiego,San
cialtycare.TheAmericanAcneandRosaceaSocietyconvenedapanel
Diego,California;bSectionofDermatology,ValleyHospital
of pediatric dermatologists, pediatricians, and dermatologists with
MedicalCenter,LasVegas,Nevada;cDepartmentofDermatology,
SUNYDownstateMedicalCenter,Brooklyn,NewYork;dPediatric/ expertise in acne to develop recommendations for the management
AdolescentDermatology,DellChildren’sMedicalCenter,Austin, of pediatric acne and evidence-based treatment algorithms.
Texas,DepartmentofDermatology,UTSouthwesternMedical
School,Dallas,TexasandDepartmentsofPediatricsand METHODS: Ten major topic areas in the diagnosis and treatment of
Dermatology,BaylorCollegeofMedicine,Houston,Texas; pediatric acne were identified. A thorough literature search was per-
eDepartmentsofDermatologyandPediatrics,Universityof formed and articles identified, reviewed, and assessed for evidence
CincinnatiCollegeofMedicineandCincinnatiChildren’sHospital
MedicalCenter,Cincinnati,Ohio;fDepartmentsofPediatricsand grading. Eachtopic areawas assignedto2 expert reviewerswho de-
Dermatology,NorthwesternUniversityFeinbergSchoolof velopedandpresentedsummariesandrecommendationsforcritique
MedicineandDivisionofDermatology,Ann&RobertH.Lurie
andediting.Furthermore,theStrengthofRecommendationTaxonomy,
Children’sHospitalofChicago;gTheRonaldO.Perelman
including ratings for the strength of recommendation for a body of
DepartmentofDermatology,NewYorkUniversitySchoolof
Medicine,NewYork,NewYork;hSectionofPediatricDermatology, evidence, was used throughout for the consensus recommendations
Children’sHospitalofPhiladelphia,Philadelphia,Pennsylvania for the evaluation and management of pediatric acne. Practical
andDepartmentsofPediatricsandDermatology,Perelman
evidence-based treatment algorithms also were developed.
SchoolofMedicineattheUniversityofPennsylvania;
iDivisionofPediatricsandHospitalMedicine,RadyChildren’s RESULTS: Recommendations were put forth regarding the classifica-
Hospital,SanDiego,CaliforniaandDepartmentofPediatrics,
tion, diagnosis, evaluation, and management of pediatric acne, based
UniversityofCalifornia,SanDiego,California;jDepartmentof
Dermatology,JeffersonMedicalCollege,ThomasJefferson onageandpubertalstatus.Treatmentconsiderationsincludetheuse
University,Philadelphia,Pennsylvania;kDepartmentof of over-the-counter products, topical benzoyl peroxide, topical
Dermatology,ThePennsylvaniaStateUniversityCollegeof
retinoids, topical antibiotics, oral antibiotics, hormonal therapy, and
Medicine;andlDepartmentofPediatrics,PennStateHershey
Children’sHospital,Hershey,Pennsylvania isotretinoin. Simplified treatment algorithms and recommendations
are presented in detail for adolescent, preadolescent, infantile, and
KEYWORDS
pediatricacne,acnetreatment,combinationacnetherapy, neonatal acne. Other considerations, including psychosocial effects
retinoids,benzoylperoxide,bacterialresistance,isotretinoin, of acne, adherence to treatment regimens, and the role of diet and
hormonaltherapy,acneguidelines,acnealgorithm,neonatal
acne, also are discussed.
acne,infantileacne,mid-childhoodacne,preadolescentacne,
AmericanAcneandRosaceaSociety,AARS CONCLUSIONS:TheseexpertrecommendationsbytheAmericanAcne
(Continuedonlastpage)
andRosaceaSocietyasreviewedandendorsedbytheAmericanAcad-
emyof Pediatrics constitutethe first detailed, evidence-basedclinical
guidelines for the management of pediatric acne including issues of
specialconcernwhentreatingpediatricpatients.Pediatrics2013;131:
S163–S186
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Acne vulgaris is one of the most com- American Acne and Rosacea Society, Each topic area was assigned to 2 ex-
mon skin conditions in children and a nonprofit organization promoting pert reviewers, who developed and
adolescents.Althoughoftenconsidered research, education, and improved presented an in-depth summary and
a disease of teenagers, in whom the careofpatientswithacneandrosacea. recommendations for further critique
prevalenceisreportedtobefrom70% The expert panel was charged with and editing. The Strength of Recom-
to 87%,1 12 years of age is no longer developing recommendations for the mendation(SOR)Taxonomyratingsfor
considered the lower end of the age management of pediatric acne and therecommendationforabodyofevi-
rangeforacneonset.2AstudybyLucky evidence-basedtreatmentalgorithms. denceisnotedthroughoutthearticle.4
et al3 revealed acne lesions in 78% of Amemberoftheexpertpanelservedas This taxonomy addresses the quality,
365girlsages9to10.Inaddition,acne liaison to the American Academy of quantity, and consistency of evidence
and other acneiform (acnelike) con- Pediatrics and as part of the recom- and allows authors to rate individual
ditions occur at different ages, in- mendationwritinggroup. studiesorbodiesofevidence.Thetax-
cluding neonates, infants, and young onomy emphasizes the use of patient-
children, and may be associated with METHODS oriented outcomes that measure
differential diagnoses or systemic pa- changesinmorbidityormortality.The
The expert panel identified special
thologythatdiffersfromteenagers. authors reviewed the bodies of evi-
issuesinthediagnosisandtreatmentof
dence for each of the recommenda-
Thereareissuesofspecialconcernin acne and acneiform conditions in pe-
tionsandassignedoneofthefollowing
treatmentofpreadolescentswithacne. diatric patients across various ages.
SOR: an A-level recommendation is
The majority of clinical trials foracne Tenmajortopicareaswerespecifiedby
based on consistent and good-quality
medicationsareconductedinpatients thepanel(Table1).AthoroughEnglish-
patient-oriented evidence; a B-level
12 years of age or older. As a result, languageliteraturesearchwasperfor-
recommendation is based on inconsis-
there is little published evidence re- medforeachtopicarea,andidentified
tent or limited-quality patient-oriented
gardingthesafetyandefficacyofmany articles were reviewed utilizing a
evidence; and a C-level recommenda-
acnemedicationsinpediatricpatients. patient-centered approach to grading
tion is based on consensus, usual
Furthermore, the treatment of acne evidenceavailabletotheexpertpanel.4
practice, opinion, disease-oriented ev-
often involves use of several medi- Relevant clinical trial registries and
idence, or case series for studies of
cationsthattargeteitherdifferenttypes data filed with the Food and Drug Ad-
diagnosis, treatment, prevention, or
of acne lesions, different factors in- ministration(FDA)wereincludedinthe
screening.Thisarticlesummarizesthe
volved in the pathogenesisof acne, or datareview.
resultant consensus recommenda-
different degrees of acne severity. Po-
tions for the evaluation anddiagnosis
tential interactions between medi-
ofpediatricacne,aswellasaseriesof
cations can add another layer of TABLE1 TopicAreasResearchedand
treatment algorithms to assist health
DiscussedbyExpertPanel
complexitytothemanagementofacne
carepractitionersinthemanagement
in pediatric patients, as can concerns PediatricAcneCategorizationandDifferential
DiagnosisofAcne and treatment of acne in pediatric
aboutsystemicsideeffectsandimpact
EvaluationofPediatricAcnebyAge/Classification patients.
of medications on growth and de-
Evidence-basedTreatmentReviewforPediatric
velopment.Thepsychosocialimpactof Acne
acnecanbesignificant,ascanissuesof (cid:129)OTCproducts CATEGORIZATION AND
adherencetotreatmentregimens. (cid:129)BPtreatment DIFFERENTIAL DIAGNOSIS OF
(cid:129)Topicalretinoids,antibiotics,andfixed-dose
PEDIATRIC ACNE
Currently,detailed,acknowledgedguide- combinationproducts
lines for the diagnosis and manage- (cid:129)Oralantibiotics:age-relatedissues,safety,and Bothageandformofpresentationare
resistance
mentofacneinpediatricpatientsare (cid:129)Isotretinoinpediatricpatientswithsevereacne relevant to the diagnosis of pediatric
lacking. Recognizing the need to ad- (cid:129)OCuseandhormonaltherapy acne.Althoughthereissomeoverlapin
dress special issues regarding the PediatricAcneTreatmentConsiderations age and presentation of acneiform
(cid:129)Previoustreatmenthistory
diagnosis and treatment of acne in (cid:129)Costs conditions,theconsensusofthepanel
children of various ages, a panel of (cid:129)Easeofuse/regimencomplexityandadherence regarding relevant age categories is
experts consisting of pediatric der- (cid:129)Vehicleselection presentedinTable2.Theserangesare
(cid:129)Activescarring
matologists, pediatricians, and der- approximate. In girls, age of onset of
(cid:129)Sideeffects
matologistswithexpertiseinacnewas (cid:129)Psychosocialimpact menarchemaybeabetterdelineating
convened under the auspices of the (cid:129)Diet point between preadolescence and
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TABLE2 ExpertPanelConsensus:Pediatric cheeks,chin,eyelids,andforehead,but mass.12Shouldworkupforahormonal
AcneCategorizedbyAge the scalp, neck, and upper chest and anomaly be considered, a pediatric
AcneType AgeofOnset back may be involved.8 Its pathogene- endocrinology referral and/or bone
Neonatal Birthto#6wk sis may involve colonization with ageandserologicevaluationoffollicle-
Infantile 6wkto#1y Malassezia species, a normal com- stimulatinghormone,luteinizinghormone,
Mid-childhood 1yto,7y
Preadolescent $7to#12yormenarche mensalofinfantskin,ormayrepresent testosterone, and dehydroepiandros-
ingirls an inflammatory reaction to a yeast teronesulfatelevelsarerecommended.
Adolescent $12to#19yorafter overgrowthatbirth.8,10NCPistypically Nofurtherworkupisnecessaryforthe
menarcheingirls
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,becausethereissomeevidence
manifestationofunderlyingpathology. bornsalsomaypresentwithordevelop thatinfantileacnepredisposestomore
It is essential to have a broad un- transientneonatalpustularmelanosis, severeadolescentacne.13Infantileacne
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.Within24hours,thesepustules bialagents;topicalretinoids;noncycline
agnoses for each age group. Table 3 rupture,leavinghyperpigmentedmac- antibiotics, such as erythromycin; and,
presents a differential diagnosis for uleswitharimoffaintwhitescale.10 occasionally,isotretinoin,thoughallare
acne in each age group.5–7 Workup is ConsensusRecommendation: without FDA indication for use in this
based on age and physical findings.6 (cid:1) agegroup.
Neonates may have true acne, al-
Thephysicalexaminationshouldfocus ConsensusRecommendation:
though many self-limited papulo-
on type and distribution of acne (cid:1)
pustular eruptions also occur on Most infantile acne is self-limited
lesions, height, weight, growth curve,
the faces of neonates. In infants andnotassociatedwithunderlying
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
maturationorvirilizationshouldprompt
ris, evaluation for signs of sexual signs of hormonal abnormality,
workupand/orareferraltoapediatric
precocity,virilization,and/orgrowth a more extensive workup and/or
endocrinologist.8
abnormalities that may indicate an referral to a pediatric endocrinol-
ConsensusRecommendation: underlying systemic abnormality ogistmaybeappropriate.(SOR:C).
(cid:1)
Acneiform eruptions from the neo- (endocrinologic diseases, tumors,
natal period through adolescence gonadal/ovarian pathology) and ap- Mid-Childhood Acne
maybebroadlycategorizedbyage propriateworkupand/orreferralto
Mid-childhoodacnepresentsprimarily
and pubertal status. a pediatric endocrinologist may be
onthefacewithamixtureofcomedones
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
Neonatalacneisestimatedtoaffectup Infantileacnemaybeginat∼6weeksof significantlevelsofadrenalorgonadal
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,foryears.Itismorecommonin group is rare. When it does occur, an
thelesionstrulyrepresentacneorone boysandpresentswithcomedonesas endocrine abnormality should be sus-
of a number of heterogeneous pap- well as inflammatory lesions, which pected. Aworkup by a pediatric endo-
ulopustularacneiformconditionstypi- can include papules, pustules, or oc- crinologistisusuallywarrantedtorule
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
transientneonatalpustularmelanosis. ment of growth including height, androgen-secretingtumors.Increased
Although rare, some neonates may weight, and growth curve; testicular bone age and accelerated growth, as
present with androgen-driven come- growthandbreastdevelopment;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 areimportantindicatorsoftheeffects
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TABLE3 DifferentialDiagnosisofAcnein than8yearsofagebecauseoftherisk ConsensusRecommendation:
YoungerPediatricandAdolescent of damage to developing bones and (cid:1) Preadolescent(7–12years)acneis
Patients
toothenamel.Hormonaltherapycould
common and may precede other
Adolescent(∼12–18yofage)
beusedifwarrantedbyendocrinologic
signsofpubertalmaturation.Workup
Corticosteroid-inducedacne
pathology.8 beyondhistoryandphysicalisgen-
Demodexfolliculitis
Gram-negativefolliculitis ConsensusRecommendation: erally unnecessary unless there
Keratosispilaris (cid:1) Mid-childhood acne is very uncom- aresignsofandrogenexcess,PCOS,
Malassezia(pityrosporum)folliculitis
or other systemic abnormalities.
Papularsarcoidosis mon and should warrant an endo-
Perioraldermatitis crinologic workup for causes of (SOR: B).
Pseudofolliculitisbarbae
hyperandrogenism. (SOR: C).
Tineafaciei
Preadolescent($7to#12yofage)
Acnevenenataorpomadeacne(fromtheuse Preadolescent Acne PEDIATRIC ACNE CLASSIFICATION
oftopicaloil-basedproducts) AND SEVERITY ASSESSMENT
Itisnotuncommonforacnevulgaristo
Angiofibromasoradenomasebaceum
Corticosteroid-inducedacne occurinpreadolescents,asaresultof Ingeneral,treatmentofpediatricacne
Flatwarts normal adrenarche and testicular/ vulgarisissimilartoacnetreatmentin
Keratosispilaris
ovarian maturation. Acne may be the older adolescents and adults and is
Milia
Molluscumcontagiosum first sign of pubertal maturation.8 In based on acne pathophysiology. The
Perioraldermatitis fact,withthetrendtowardearlierage pathogenesis of acne involves the in-
Syringomas ofonsetofadrenarcheandmenarche, terplay of 4 factors: sebaceous hyper-
Mid-Childhood(1–7yofage)
thereappearstobeadownwardshift plasiaundertheinfluenceofincreased
Adrenaltumors
Congenitaladrenalhyperplasia intheageatwhichacnefirstappears. androgenlevels,alterationsinfollicular
Cushingsyndrome Preadolescentacneischaracterizedby growthanddifferentiation,colonization
Gonadaltumors
a predominance of comedones on the of the follicle by Propionibacterium
Ovariantumors
PCOS forehead and central face (the so- acnes (P acnes), and consequent im-
Prematureadrenarche called “T-zone”) with relatively few in- muneresponseandinflammation.15
Trueprecociouspuberty flammatory lesions.10 Early pre- Ausefulclinicalcategorizationofacne
AnyAge
Acnevenenataorpomadeacne(fromtheuseof sentation may include comedones of is based on predominate morphology:
topicaloroil-basedproducts) theear. comedonal with closed and open
Bilateralnevuscomedonicus
History and physical examination are comedones (“whiteheads” and “black-
Chlorinatedaromatichydrocarbons(chloracne)
Corticosteroids(topical,inhaled,andoral) the most important parts of the as- heads”);inflammatory,witherythema-
Demodicidosis sessment in this age group. Further tous papules, nodules, or cystlike
Facialangiofibromas(tuberoussclerosis)
workup is generally unnecessary un- nodularlesions;ormixed,whereboth
Flatwarts
Infections(bacterial,viral,andfungal) less there are signs of excess andro- typesoflesionsarepresent.Themicro-
Keratosispilaris gens.7 Polycystic ovary syndrome comedo is the not-clinically-apparent
Medication-Induced(anabolicsteroids,
(PCOS) or another endocrinologic ab- precursor of both comedonal and in-
dactinomycin,gold,isoniazid,lithium,phenytoin,
normalitymaybeconsideredwhenthe flammatorylesions.Itisaproductofhy-
andprogestins)
Milia acneisunusuallysevere,accompanied peractive sebaceous glands and altered
Miliaria by signs of excess androgens, or is follicular growth and differentiation.
Molluscumcontagiosum
Periorificialdermatitis unresponsivetotreatment.14Pelvicul- Reductioninexistingmicrocomedones
Rosacea trasound is not considered useful for andpreventionoftheformationofnew
AdaptedfromTomandFriedlander6andKrakowskiand diagnosis of PCOS because it is non- ones is central to the management of
Eichenfield.7 specific. allacnelesions.16
Treatment of uncomplicated pre- Comedones form as a result of in-
ofexcessandrogens.Inadditiontotreat- adolescentacneiscomparabletothat creasedcelldivisionandcohesiveness
ments to address androgen-secreting of acne in older age groups, as dis- ofcellsliningthefollicularlumen.When
tumors or congenital adrenal hyper- cussedlater.Itisimportantinthisage thesecellsaccumulateabnormally,mix
plasia,thetreatmentofmid-childhood group to elicit the patient’s level of withsebum,andpartiallyobstructthe
acne is similar to that of adolescent concern regarding his or her acne, follicular opening, they form a closed
acneexceptthatoraltetracyclinesare which may not always be concordant comedo (whitehead). If the follicular
usuallynotanoptioninchildrenyounger withparentalconcern. openingislarger,thekeratinbuildupis
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morevisibleandcandarkentoforman treatment as patients may not recog- Although no single acne treatment,
open comedo (blackhead). Follicular nize the improvement or think they apartfromisotretinoin,addressesall4
colonization with P acnes leads to in- have scarring. Effective and early pathogenicfactors,itisnowclearthat
flammationviatheproductionofinflam- treatment is essential to prevent many of the medications traditionally
matorymediatorsandtheformationof scarringaswellaspostinflammatory usedtotreatacneactuallyactbymore
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. genicfactors,theapproachtopediatric
nodules or pseudocysts and is often It has been repeatedly demonstrated acne should be to use the least ag-
accompaniedby scarringor thepres- thatacnecanhaveasignificantadverse gressiveregimenthatiseffectivewhile
ence of sinus tracts when adjacent impact on quality of life, and that the avoiding regimens that encourage the
nodulescoalesce. level of distress may not correlate di- development of bacterial resistance.
Acne severity may be classified clini- rectlywithacneseverity.18,19In1study, Educatingapatient(andparents)about
reasonableexpectationsofresultsand
callyasmild,moderate,orseverebased assessments using several quality of
onthenumberandtypeoflesionsand life instruments revealed deficits for discussing management of treatment-
related side effects can maximize
the amount of skin involved. Although acne patients who did not correlate
bothcomplianceandefficacy.
therearenumerousgradingsystemsby withclinicalassessmentsofseverity.20
whichtodefineacneseverity,thereisno Reported social, psychological, and Numerousmedicationsareavailableto
agreed-upon standard, and interpre- emotionalsymptomswereassevereas treatacne.Designofaneffectiveregi-
tationissubjective.Manygradingsys- 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- chronicasthma,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
particular,maybeinsecureabouttheir keyantiacneagentsdiscussedlater.
sessments do not correlate well with
appearance and vulnerable to peer
eitherthoseofphysiciansorpublished
severityscales.17Thepanelnotedthat opinions. Because social functioning OVER-THE-COUNTER TREATMENT
severityscalesfrequentlyoveremphasize andquality-of-lifedecrementsmaynot OPTIONS
inflammatorylesions.Forexample,in correlate with disease severity, even
Nationwide television commercials and
mild acne may be more troubling to
some research settings, a patient
magazine ads abound with over-the-
might be classified as having mild youngpatientsthantheyarewillingto counter(OTC)products.Althoughlargely
admit.21
acnebecauseheorshehasonlyafew untested in controlled clinical trials,
inflammatory lesions in the presence ConsensusRecommendation: manyoftheseproductsareconsidered
of hundreds of closed comedones. In (cid:1) 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-
extentofinvolvementandscarringas ity may be broadly categorized as scribed in further detail later. Salicylic
well. mild,moderate,orsevere.(SOR:A). acidhasrevealedsomeefficacyinacne
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) Thetherapeuticobjectivesinacneare products appear to be somewhat ef-
is common. Residualerythema can oc- to treat as many age-appropriate fectivefor thetreatmentofacne,espe-
cur as well. These changes are most pathogenic factors as possible by re- ciallymildacne,thoughthereislimited
often reversible but can take many ducing sebum production, preventing published evidence supporting their
months to fully resolve. Recognizing the formation of microcomedones, efficacyinthetreatmentofacne.
these as secondary changes is impor- suppressingPacnes,andreducingin- Sulfur, sodium sulfacetamide, and
tant when determining the efficacy of flammationtopreventscarring. resorcinol are active ingredients in
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several OTC dermatology niche prod- mits it to penetrate the stratum cor- short-contact BP therapies do not sig-
ucts.Sulfurexhibitsmildantibacterial neumandenterthepilosebaceousunit nificantlyreducebacterialload,butdata
and keratolytic properties.24 Because where Pacnes resides. It acts via the arelacking.However,theycanbeeffec-
of sulfur’s distinctive odor, it is often generation of free radicals that oxi- tive if left on the skin for the duration
combined with sodium sulfacetamide dizeproteinsinthePacnescellwall. recommendedbythemanufacturer.
tomaskthescent.25Itisoftenusedin It also has been shown to have mild ConsensusRecommendations:
adult female acne because of its fa- comedolytic36 and antiinflammatory (cid:1) BP is generally regarded as a safe
vorabletolerability.26,27Resorcinolalso
properties.37,38 BP helps limit the de- and effective medication that may
hasmildantimicrobialpropertiesand
velopment of P acnes resistance to be usedas monotherapyor in top-
is typically formulated in a 2% con-
antibiotics and also provides increased ical combination products for mild
centration in combination with 5%
efficacyincombinationwithretinoids.39,40 acne or in regimens of care for
sulfur.
So far, antibiotic resistance to BP has acne of all types and severities.
One common acne myth is that poor notbeenreported.41–44 (SOR: A).
hygieneandimpropercleansingcause (cid:1)
Althoughissuesregardinggenotoxicity BP may minimize development of
acne.21,28Theroleoffacialcleansingin
havebeenraisedinthepast,BPhasnow antibiotic-resistant P acnes when
acne is to remove makeup, dirt, and
been labeled as “GRASE” (generally used with topical or systemic anti-
excess oil.29 Use of the wrong, too
regardedassafeandeffective)bythe biotics. (SOR: C).
harsh cleanser can disrupt skin bar-
FDA, and all topical monotherapy
rier, increase transepidermal water
productshavebeenmadeavailableOTC
loss, encourage bacterial coloniza- PRESCRIPTION TREATMENT
since2011.Labelingincludesadviceto
tion, promote comedones, and cause OPTIONS: SINGLE AGENTS
avoid the eyes, lips, and mouth. The
symptomsofburningandstinging.30,31 Topical Retinoids
product can cause bleaching of hair
Typically, twice-daily washing with a
and clothing, and risk of increased Topicalretinoids,asmonotherapyand
gentlesoap-free,pH-balancedcleanser
sunburn and the need for photo- in topical combination products, are
isrecommended.Antibacterialwashes,
protectionalsoarementioned.BPfre- usedroutinelyforthetreatmentofacne
other thanBP,havenotbeenshownto
quentlycausesdryness,erythema,and vulgaris. Their safety and efficacy are
beusefulinthetreatmentofacne.
peeling upon initiation of treatment. welldocumentedinlargepivotaltrials
Facialtonerscandecreaseoilinessand
Startingwithlowerconcentrations(eg, thatincludedpediatricpatientsranging
removemakeupandtracesofdirt.They
2.5%) and utilizing more emollient from 12 to 18 years of age. Sub-
are a common component of several
vehicles if needed can help alleviate sequently, because acne routinely
prepackaged combination acne treat-
these discomforts. Allergic contact presents in patients younger than 12
mentregimens.Patientsshouldbecau-
dermatitis to BP occurs in 1 in 500 years of age, topical retinoids are
tious not to overuse facial toners
people and should be considered if widelyusedoff-labelinthisagegroup.
becausetheycanbeirritating.Ifirritation
a patient complains of itching and Tretinoingel0.05%(Atralin,CoriaLab-
occurs, this will adversely affect the
swellingoftheeyes. oratories, Fort Worth, TX) is FDA-
tolerabilityofacnemedications. approvedforuseinchildren$10yearsof
BP is available in a variety of for-
Anothercommonacnemythisthatuse mulationsandinconcentrationsrang- age,46 and adapalene and benzoyl per-
of cosmetics worsens acne. On the oxide gel 0.1%/2.5% (Epiduo, Galderma
ing from 2.5% to 10%. There is some
contrary, use of concealing oil-free, Laboratories, LP, Fort Worth, TX) is in-
evidencethathigherconcentrationsdo
noncomedogenic makeup can im- not increase efficacy but are more ir- dicatedforages9andolder.Adapalene
provepatientqualityoflifeanddoesnot gel, tretinoin gel, and tretinoin micro-
ritating. However, the back may be
worsentheseverityofacne.32,33Useof a “special site” circumstance, where sphere gel have been investigated in
cosmeticsinpatientswithacnehasnot both open-label and blinded studies in
increasingconcentrationorprolonged
been shown to delay treatment re- contact leads to increased efficacy.45 childrenunder12yearsofage.47–49
sponseeither.
Formulationsinclude avarietyoftopi- Retinoids normalize desquamation of
BP has been shown to be the most cal leave-on preparations as well as thefollicularepithelium,thuspreventing
widelystudiedofOTCproductsandhas washesthatpermitpatientstoremove theformationofnewmicrocomedones,
showntobeoneofthemostversatile, BP from the skin, reducing the possi- precursorstobothcomedonalandin-
safe, inexpensive, and effective acne bilityofbleachingofclothing,bedding, flammatorylesions, andalso promote
therapies.34,35Itslipophilicnatureper- or towels.38 It has been suggested that theclearingofexistingmicrocomedones.50
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In addition, some topical retinoids TABLE4 FormulationsandConcentrationsofTopicalRetinoids
also have direct antiinflammatory Retinoid Formulationa Strength,% PregnancyCategory
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
tazarotene) are available by pre- Gel(micronized) 0.05
Microspheregel 0.04,0.1
scriptionintheUnitedStates.Eachis
Polymerizedcream 0.025
available in a variety of formulations Polymerizedgel 0.025
and concentrations (Table 4).53 Their Adapalene Cream 0.1 C
Gel 0.1,0.3
mostcommonadverseeffectsinclude
Solution 0.1
burning, stinging, dryness, and scal- Lotion 0.1
ing.15Theseeffectsmaybereducedby Tazarotene Gel 0.05,0.1 X
Cream 0.05,0.1
initiating treatment with the lowest
strength, typically sufficient to treat AdaptedfromImahiyerobo-IpandDinulos.52
aNumerousgenericretinoidsareavailable.Brandedproductsareavailableunderthefollowingtradenames:Atralin,Avita,
mildacne,orbyrecommendingregular andRetin-AMicrofortretinoin;Differinforadapalene;andTazoracfortazarotene.
useofamoisturizer.Patientsshouldbe
instructednottospot-treatbutratherto
areextremelyrareintheliterature,in a study of 215 women accidentally ex-
useapea-sizeamounttocover theen-
a 16-week study of 12 infants with in- posed to topical tretinoin during the
tireface.Inpatientswithsensitiveskin,
fantile acne (mean age, 12.6 months), firsttrimesterofpregnancy,Jicketal57
therapy can be initiated with thrice-
0.1% adapalene cleared both come- showednodifferenceindevelopmental
weekly application, increasing to daily
donal and inflammatory lesions in anomalies compared with 430 age-
useastolerated.48
amedianof3.4monthswithsideeffects matched controls. Tretinoin and ada-
Tolerabilitymaybefurtherimprovedby
that did not require discontinuation, palene have a pregnancy category C
the use of a noncomedogenic moistur-
underscoring the reported high toler- andtazaroteneacategoryXrating.
izer thatincludesasunscreen.15,38Top-
abilityofadapalene.47Tazaroteneisan ConsensusRecommendation:
ical tretinoin was the first retinoid
effectivetopicalretinoid,butitisused (cid:1)
approvedforuseintheUnitedStates.It Topical retinoids (tretinoin, adapa-
lessoftenasafirst-lineagentforacne
isavailableinavarietyofvehiclessuch lene, tazarotene) may be used as
becauseofconcernsregardingtolera-
as a micronized gel or a polymerized monotherapy or in combination
bility;itisalsoknowntobemoreirri-
cream for increased tolerability. In a products and in regimens of care
tating.56
12-weekopen-labelstudyof40patients forall types and severities of acne
In the absence of significant systemic
with mild/moderate acne ages 8 to 12 in children and adolescents of all
absorptionoftheactiveingredients,the
years (mean age,10.7years), tretinoin ages.(SORadolescents:A;SORpre-
possibilityofintolerabilityremainsthe
microspheregel0.04%producedasig- adolescents and younger: B).
primary safety issue. However, older
nificant decrease in Evaluator’s Global
girls who may be of childbearing po-
SeverityScore(P,.001)frombaseline Antibiotics/Antimicrobials
tential are often of the age group
to week 12, with 75% of participants
Although acne is not an infection,
treatedwithtopicalretinoids.Naturally
graded as almost clear or mild. Skin
antibioticsreducePacnescolonization
circulating endogenous retinoids are
irritation occurred in 35% of the
of the skin and follicles. They are ef-
presentintheplasmaofnormalhealthy
patientsbutwasmildinmostcasesand
girlsasaresultofdietaryconsumption fective in acne both by inhibiting bac-
improvedbystudy’send.48 of foods such as fish, carrots, sweet terial protein synthesis38 and by
Other topical retinoid alternatives potatoes,andredpeppers.Continuous decreasinginflammationviainhibition
to tretinoin include adapalene and of bacterial proinflammatory media-
daily dosing of tretinoin 0.1% cream,
tazarotene. Adapalene, a distinct reti- tors and decreasing neutrophil che-
tazarotene 0.1% gel, and adapalene
noidthatisgenerallywelltolerated,is 0.1%gelhasbeenshowntoonlyslightly motaxis.58,59
available in cream, gel, and lotion
increase the mean maximum plasma The alarming increase in P acnes re-
formulations.53,54 Adapalene is photo- levels of circulating retinoids in most sistance to both topical and systemic
stable, including in fixed-combination
patients. In 1 study, serum retinoid antibioticsusedtotreatacnenotonly
withBP.55 levels were found to be more heavily renders these drugs less effective
Although studies regarding the use of influenced by dietary intake than by against acne but may also influence
topical retinoids in pediatric patients topical application of tretinoin. In commensal bacteria in both the acne
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patient and his or her environment.60 (administeredas1tabletdaily)isFDA mostcommonwithoraldoxycycline.73–75
Resistance may occur with both ap- approved for the treatment of moder- Theformercanbecircumventedwith
propriate and incorrect use of anti- ate to severe inflammatory acne vul- appropriate photoprotection, and the
biotics.58 garisthatisnotpredominantlynodular latter by ingestion with a large glass
in patients $12 years of age.62 Both of water, maintaining an upright posi-
Topical Antibiotics immediate-release doxycycline and tionforatleast1 hourafter ingestion,
Topical antibiotic monotherapy is not immediate-release minocycline have and use of an enteric-coated formula-
recommendedbecauseofbothitsslow listed the indication in their FDA- tion.76 Although rare, drug hypersensi-
onset of action and the greater likeli- approved labeling of adjunctive use tivitysyndrome(DHS),Stevens-Johnson
hood of the development of bacterial forsevereacne,althoughthiswasnot syndrome,orlupuslikesyndrome(LLS)
resistance. If topical or oral antibiotic based on formal submission for FDA may occur with administration of
treatmentistobeprolongedmorethan approvalforeitherdrug.63,64 Thecom- minocycline.DHSpresentsearlyafter
afewweeks(asis usuallythecasein monlyusedoralantibioticsforchildren initiationofminocyclinetherapy,usu-
acne treatment), topical BP should be older than 8 years are tetracycline ally within the first 2 to 8 weeks,
added to optimize efficacy via its non- derivatives, including tetracycline, commonly with flulike symptoms (ie,
specific antimicrobial activity and re- doxycycline,andminocycline.Although fever, malaise), diffuse exanthemlike
duce the emergence of less sensitive erythromycinwasusedsuccessfullyin erythema,facialedema,cervicallymph-
P acnes variants.60 It has even been the past, the worldwide prevalence of adenopathy, and elevated hepatic en-
suggested that, if antibiotic therapyis P acnes resistance to erythromycin zymes (especially transaminases),
maintained for more than 3 months, hasledtodecreaseduseofthisagent, although other organs may be in-
a BP washout should occur between bothorallyandtopically,foracne.60,65,66 volved with interstitial inflammation
courses, although no large studies Comparative studies are limited, but (eg, pneumonitis, nephritis, and thy-
have addressed this recommenda- the second-generation tetracyclines, roiditis).77,78
tion.15 doxycycline and minocycline, are pre- Minocycline-associated LLS, which is
Use of topical antibiotics in fixed- ferred because of pharmacokinetic commonly reversible, generally devel-
combination products containing BP advantages allowing for once-daily ops after chronic exposure (ie, many
may help reduce the emergence of administration in most cases, greater months to years), and often presents
antibiotic-resistantstrainsofbacteria. lipophilicitythatisbelievedtoaugment with malaise, distal polyarthralgias
Inthecaseofthefixed-combinationof follicular penetration, and lower prev- withorwithoutpolyarthritis,and,more
tretinoinandclindamycin,concomitant alence of resistant Pacnes strains as rarely,autoimmunehepatitis.78–80Most
useofBPisrecommended. compared with tetracycline.15,67,68 For casesofminocycline-associatedLLSdo
ConsensusRecommendation: children under 8 years of age and nothaveskineruptions,althoughrare
(cid:1) Topical antibiotics (clindamycin, those with tetracycline allergies, al- reports have revealed superficial vas-
erythromycin) are not recommen- ternative oral antibiotic agents, in- culitissuchascutaneouspolyarteritis
ded as monotherapy because of cluding erythromycin, azithromycin, nodosa.Apositiveantinuclearantibody
slowonsetofactionandpredictable and trimethoprim/sulfamethoxazole, testisoftenpresent,althoughnotalways
emergence of antibiotic-resistant should be used very judiciously be- diagnostic or predictive of minocycline
bacterial organisms. (SOR: C). If cause of the potential risk for severe LLS, along with other autoantibodies.
topical antibiotic treatment is to adverse reactions, such as toxic epi- Theautoantibodyprofilemaybehighly
be prolonged for more than a few dermal necrolysi.69–72 Table 5 sum- variable among cases of minocycline-
weeks, topical BP should be added, marizes the dosages, adverse events, associated LLS. When present, p-anca
or used in combination products. andprecautionsregardingtheuseof positivity is believed to strongly sup-
(SOR: C). the most frequently used oral anti- portthediagnosis.Presenceofantihi-
bioticsfor treatmentofinflammatory stone antibody is not required to
Oral Antibiotics acne.69 confirm the diagnosis of LLS and may
Interestingly, with the exception of The panel agreed that education and notbedetectedinsomecases.Finally,
extended-release minocycline, use of monitoringrelatedtopotentialadverse within the first few weeks of minocy-
oral antibiotics in acne is not FDA ap- eventsisimportantwithoralantibiotic cline treatment,physiciansshouldcon-
proved.61 Extended-release minocy- therapy for acne. Photosensitivity (pho- sidertherareriskofserumsicknesslike
cline dosed at 1 mg/kg per day totoxicity) and “pill esophagitis” are reaction.78 Cutaneous and/or mucosal
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TABLE5 OralAntibioticsUsedforTreatmentofModerate-to-SevereAcneVulgaris
Antibiotic RecommendedDosage PotentialAdverseEffects Comments
Doxycyclinea 50–100mgQDorBID; Gastrointestinalupsetespeciallypill Canbetakenwithmeals,takewithlargeglass
150mgQD esophagitis(reducedwithentericcoated ofwaterandmaintainuprightposition$1h
formulation);photosensitivity(especiallyin todecreaseriskofesophagitis;optimize
dosesof$100mgdaily);stainingof photoprotectionespeciallyinsunnyseason
formingtoothenamel(ifgiven#8yofage); orwithknownincreasedoutdoorexposure;
vaginalcandidiasis;BIH(rare). avoidinchildrenwhohavenotdeveloped
setofpermanentteeth;monitorforblurred
vision,severeheadachessometimeswith
nauseaand/orvomiting.
Erythromycinb 250–500mgQD-BID Gastrointestinalupset;drug-druginteractions Highprevalenceofantibiotic-resistantPacnes.
suchasincreaseincarbamazepineserum
levels→toxicity.
Tetracycline 500mgBID Fixeddrugeruption;gastrointestinal Ingestonemptystomachpreferable;
symptoms;stainingofformingtoothenamel absorptionisdecreasediftakenwithiron,
(ifgiven#8yofage);vaginalcandidiasis; calcium,ormanyothermetalionsfoundin
BIH(rare). vitamins/supplements,dairyproducts
(includingmilk,yogurt);avoidinchildren
whohavenotdevelopedsetofpermanent
teeth;avoidinrenalorhepaticdisease;
monitorforblurredvision,severe
headachessometimeswithnauseaand/or
vomiting.
Minocycline(immediaterelease) 50–100mgQD-BID Cutaneousand/ormucosalhyperpigmentation Canbetakenwithmeals;warnpatientabout
ofskinandmucosalsites(oral,sclera, dizziness/vertigo(suggestinitialdosesbe
conjunctiva);bonemaybeaffectedinsome givenwhenathomeandnotdrivingto
cases;DHS(systemic)oftenwithhepatitis assessifpatientsusceptibletothese
and/orpneumonitis(mostoftenwilloccur effects);avoidinchildrenwhohavenot
withinthefirst1–2mo);hepatitis developedsetofpermanentteeth;monitor
(hypersensitivity[tendstooccurmore formalaise,flulikesymptoms,diffuse
acutelyearlyintreatmentcourse]or erythemawithfacialswelling,respiratory
autoimmune[moreoftentooccurwith complaintssuggestiveofdrug
morechronicuseofseveralmonthsto hypersensitivityespeciallywithinthefirst
years]);LLS;Stephens-Johnsonsyndrome; fewmonthsafterstartingtherapy;
vestibulartoxicity(tendstooccurwithinthe discontinuetherapyifthissideeffect
firstfewdaysafterstartingtherapy); suspected;monitorformalaise,distal
stainingofformingtoothenamel(ifgiven arthralgiaswithorwithoutarthritis
#8yofage);vaginalcandidiasis;BIH(rare). especiallywithmoreprolongeduseof
severalmonthstoyearssuggestiveofLLS;
monitorforpigmentarychangesonskin
especiallyface,trunk,legs,andscars;
monitorforblueorgraydiscolorationof
sclera,oralmucosa,nailbeds;monitorfor
bluediscolorationofacnescars;somecases
maybepersistentevenwithdiscontinuation;
monitorforblurredvision,severe
headachessometimeswithnauseaand/or
vomiting.
Minocyclineextended-releasetablets 1mg/kgQD Samepotentialreactionsasabovealthough Sameasaboveexceptlowerincidenceofacute
(availablesince2006) abovesideeffectsreportedpredominantly vestibularsideeffectswithweight-based
withimmediate-releaseformulations dosing(1mg/kgperday);notyetknownif
(availablesince1971);lowerincidenceof otherpotentialsideeffectsreducedwith
acutevestibularsideeffectswithweight- weight-baseddosingoftheextended-
baseddosing(1mg/kgperday). releaseformulation;lessaccumulationof
minocyclineovertimedueto
pharmacokineticpropertiesofextended-
releaseformulation;maypossiblycorrelate
withdecreasedriskofcutaneousor
mucosalhyperpigmentationifdosed
properlybypatientweight.
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TABLE5 Continued
Antibiotic RecommendedDosage PotentialAdverseEffects Comments
Trimethoprim/sulfamethoxazole 160–800mgBID Severecutaneouseruptions(toxicepidermal Notgenerallyrecommendedforuseasfirstor
necrolysis,Stevens-Johnsonsyndrome); second-lineagentforacne;tobeused
bonemarrowsuppression(anemias, judiciouslyinselectedrefractorycases;
neutropenia,andthrombocytopenia); obtaincompletebloodcellcountatbaseline
hypersensitivityreactions;drugeruptions andperiodicallythereafter;additional
(rash);fixeddrugeruption. cautioninpatientswithhistoryofanemia
(megaloblastictypes);maywarrant
hematologicconsultationifuseofthisagent
highlyconsidered.
BID,twicedaily;QD,oncedaily.AdaptedfromTan,69Gollnicketal,15andDelRossoandKim.70
aEnteric-coatedanddouble-scored150mgtabletavailable;double-scoredtabletprovides50mg/unit(tabletcanbeadministeredwholeorbrokenintototalof3segments).
bUseoflowerdoseformaintenancetherapybasedonanecdotalexperienceorclinicalimpressionandnotbylarge-scaleclinicaltrials.
hyperpigmentationmayoccurinsome alsoreferredtoaspseudotumorcerebri. (cid:1) Second-generation tetracyclines
patientstreatedwithminocyclineand Ahighindexofsuspicioniswarranted (doxycycline,minocycline)aresome-
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 causeofeaseofuse,fewerproblems
casesreportedwithuseofimmediate- and/orvomiting,arenotedtodetectBIH withabsorptionwithfoodandmin-
release minocycline formulations av- early because persistence can lead to eralsinvitaminsandothersupple-
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)usingtheextended-releasetablet In the past 20 years, Pacnes has be- (cid:1) Patients should be educated and
formulationoncedaily,availablesince 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-
riskofhyperpigmentationasboththe selectionpressurearisingfromtheir 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,asyntheticsulfone,hasanti-
formulations;however,continuedphar- velopmentofresistancetoantibiotics microbialandantiinflammatoryeffects;
macosurveillance is warranted to con- whenusedtotreatacne,especiallyas
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. temic antibiotics for acne treatment TABLE6 StrategiestoOptimizeOral
AntibioticTherapyinAcneVulgaris
Acute vestibular adverse events (ie, also may be associated with an in-
vertigo, dizziness) that sometimes crease in resistant coagulase-negative Useinmoderateorsevereinflammatoryacne
vulgarisincombinationwithatopicalregimen
occur in patients treated with mino- staphylococci and a possible in-
thatincludesBP.
cyclinedevelopearlyafterinitiationof creased risk of upper respiratory Avoidantibioticmonotherapywhenusingeitheran
treatment and are reversible with tract infection; however, further oralortopicalantibioticagentforacnevulgaris.
Discontinue(ortaper)within1to2mooncenew
discontinuation of therapy.85–87 Weight- studies are needed to evaluate the inflammatoryacnelesionshavestopped
based dosing of extended release- true clinical implications of these po- emerging.
minocycline (1 mg/kg once daily) has tentialrisks.60,90 Incorporateatopicalretinoidintotheregimen
earlytoaugmentoveralltherapeuticbenefitand
been reported to reduce the risk for ConsensusRecommendations:
preparefordiscontinuationoforalagentwith
development of acute vestibular ad- (cid:1) Oral antibiotics are appropriate goalofmaintainingcontrolwithtopical
verseeventsascomparedwitha daily for moderate-to-severe inflamma- program;mayalsouseBP-containing
formulationwithtopicalretinoidfor
doseuptothreefoldhigher.61 tory acne vulgaris at any age. Tet- maintenanceofcontrolofacne.
A rare central nervous system-related racyclinederivatives(tetracycline, Ifretreatmentisneeded,usethesameoral
antibioticthatwaspreviouslyeffectiveinthe
side effect associated with use of tet- doxycycline,andminocycline)should
past.
racycline,doxycycline,orminocyclineis notbeusedinchildrenyoungerthan
AdaptedfromGollnicketal,15Leyden,50andDelRossoand
benignintracranialhypertension(BIH), 8 years of age. (SOR: B). Kim.70
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