Guidelines of care for acne vulgaris management

13 Pages·00.22 MB·English

F
ROM THE ACADEMY
Thisreportreflectsthebestavailabledataatthetimethereportwasprepared,butcautionshouldbeexercised
in interpreting the data; the results of future studies may require alteration of the conclusions or
recommendations set forth in this report.
Guidelines of care for acne vulgaris management
Work Group: John S. Strauss, MD, Chair,a Daniel P. Krowchuk, MD,b James J. Leyden, MD,c
Anne W. Lucky, MD,d Alan R. Shalita, MD,e Elaine C. Siegfried, MD,f Diane M. Thiboutot, MD,g
Abby S. Van Voorhees, MD,c Karl A. Beutner, MD, PhD,h Carol K. Sieck, RN, MSN,i
and Reva Bhushan, PhDi
Iowa City, Iowa; Winston-Salem, North Carolina; Philadelphia, Pennsylvania; Cincinnati,
Ohio; Brooklyn, New York; St Louis, Missouri; Hershey, Pennsylvania;
Palo Alto, California; and Schaumburg, Illinois
Disclaimer: Adherence to these guidelines will not ensure successful treatment in every situation.
Furthermore,theseguidelinesshouldnotbedeemedinclusiveofallpropermethodsofcareorexclusiveof
othermethodsofcarereasonablydirectedtoobtainingthesameresults.Theultimatejudgmentregarding
the propriety of any specific therapy must be made by the physician and the patient in light of all the
circumstances presented by the individual patient.
From the Department of Dermatology, Roy J. and Lucille A. Bradley/Doakreceivinghonoraria;servedontheAdvisoryBoard
CarverCollegeofMedicine,UniversityofIowa,IowaCitya;the andwasaconsultantforCollagenex,receivinghonoraria;was
Departments of Pediatrics and Dermatology, Wake Forest aconsultantandinvestigatorforConneticsreceivinggrantsand
University School of Medicine, Brenner Children’s Hospital, honoraria;anAdvisoryBoardmember,consultant,investigator,
Winston-Salemb; the Department of Dermatology, University and speaker for Galderma receiving grants and honoraria;
ofPennsylvaniaHospital,Philadelphiac;theDivisionofPediatric a consultant, speaker, and stockholder for Medicis receiving
Dermatology, Cincinnati Children’s Hospital Medical Center honoraria; an Advisory Board member for Ranbaxy receiving
and University of Cincinnati School of Medicine, Cincinnatid; honoraria;andaconsultant,investigator,andspeakerforStiefel,
theDepartmentofDermatology,StateUniversityofNewYork receivinggrantsandhonoraria.DrSiegfriedwasaninvestigator
Downstate Medical Center, Brooklyne; the Department of forAtrixreceivingsalary.DrThiboutotservedontheAdvisory
Dermatology,StLouisUniversitySchoolofMedicine,StLouisf; Board and was an investigator and speaker for Allergan and
the Department of Dermatology, Pennsylvania State Galderma,receivinghonoraria;wasontheAdvisoryBoardand
University College of Medicine, Milton S. Hershey Medical was a consultant and investigator for Collagenex receiving
Center,Hersheyg;AnacorPharmaceuticals,Inc,PaloAltoh;and honoraria;wasontheAdvisoryBoardandwasaninvestigator
theAmericanAcademyofDermatology,Schaumburg.i for Connetics, Dermik,and QLT, receiving honoraria;and was
Clinical Guidelines Task Force: Karl A. Beutner, MD, PhD, Chair, a consultant, investigator, and speaker for Intendis, receiving
MarkA.Bechtel,MD,MichaelE.Bigby,MD,CraigA.Elmets,MD, honoraria.DrVanVoorheesservedontheAdvisoryBoardand
StevenR.Feldman,MD,PhD,JoelM.Gelfand,MD,BradP.Glick, was an investigator and speaker for Amgen, receiving grants
DO,MPH,CindyF.Hoffman,DO,JudyY.Hu,MD,JacquelineM. and honoraria; was an investigator for Astellas, Bristol Myers
Junkins-Hopkins,MD,JeannineL.Koay,MD,GaryD.Monheit, Squibb,andGlaxoSmithKline,receivinggrants;wasanAdvisory
MD, Abrar A. Qureshi, MD, MPH, Ben M. Treen, MD, Carol K. Board Member and investigator for Genentech and Warner
Sieck,RN,MSN. Chilcott, receiving grants and honoraria; was on the Advi-
Fundingsources:None. sory Board for Centocor receiving honoraria; was a speaker
Disclosure:DrStrausswasaconsultantandinvestigatorforRoche for Connetics receiving honoraria; and was a stockholder
Laboratoriesreceivinghonorariaandgrants,andaconsultant ofMerck,owningstockandstockoptions.DrBeutnerwasan
for Medicis receiving honoraria. Dr Krowchukhas no relevant employee of Anacor receiving salary and stock options and
conflictsofinteresttodisclose.DrLeydenwasaconsultantfor astockholderofDowPharmaceuticalSciencesreceivingstock.
Stiefel and SkinMedica, receiving honoraria; served on the MsSieckandDrBhushanhavenorelevantconflictsofinterest
AdvisoryBoardandwasaconsultantforGaldermaandObaj, todisclose.
receiving honoraria; was on the Advisory Board and was a Reprints not available from the authors; available for download
consultantandinvestigatorforConnetics,Collagenex,Allergan, on the American Academy of Dermatology Web site:
andMedicis,receivinghonoraria.DrLuckywasaninvestigator www.aad.org.
forConnetics,Dow,Galderma,Healthpoint,Johnson&Johnson, PublishedonlineFebruary6,2007.
QLT, and Stiefel, receiving grants and an investigator and JAmAcadDermatol2007;56:651-63.
consultantforBerlexreceivinggrantsandhonoraria. DrShalita 0190-9622/$32.00
was a consultant, investigator, stockholder, and speaker for ª2007bytheAmericanAcademyofDermatology,Inc.
Allergan, receiving grants and honoraria; a consultant for doi:10.1016/j.jaad.2006.08.048
651
652 Straussetal JAMACADDERMATOL
APRIL2007
INTRODUCTION/METHODOLOGY but not the consequences of disease, including
Aworkgroupofrecognizedexpertswasconvened the scarring, post-inflammatory erythema, or post-
todeterminetheaudiencefortheguidelines,define inflammatory hyperpigmentation. The topic of light
thescopeoftheguidelines,andidentifynineclinical and laser therapy will be the subject of another
questionstostructuretheprimaryissuesindiagnosis guideline.
andmanagement.Workgroupmemberswereasked
Definitions
tocompleteadisclosureofcommercialsupport,and
Acnevulgarisisachronicinflammatorydermato-
this information will be in the acne technical report
siswhichisnotableforopenand/orclosedcomedo-
availableonwww.aad.org.
nes(blackheadsandwhiteheads)andinflammatory
An evidence-based model was used and some
lesionsincludingpapules,pustules,ornodules.
evidencewasobtainedbyavendorusingasearchof
MEDLINEandEMBASEdatabasesspanningtheyears
Issues
1970 through 2006. Only English-language publica-
The task force identified the following clinical
tionswerereviewed.
issues relevant to the management of acne: grading
The available evidence was evaluated using a
and classification; the role of microbiologic and
unified system called the Strength of Recommenda-
endocrine testing; and the efficacy and safety of
tion Taxonomy (SORT) developed by editors of
various treatments, such as topical agents, systemic
the US family medicine and primary care journals
antibacterial agents, hormonal agents, isotretinoin,
(ie, American Family Physician, Family Medicine,
miscellaneoustherapies,complementary/alternative
Journal of Family Practice, and BMJ-USA). This
therapies,anddietaryrestriction.
strategywassupportedbyadecisionofthe Clinical
Guidelines Task Force in 2005 with some minor I. SYSTEMS FOR THE GRADING AND
modifications for a consistent approach to rating CLASSIFICATION OF ACNE
the strength of the evidence of scientific studies.1 TableIshowstherecommendationsforagrading
Evidencewasgradedusingathree-pointscalebased andclassificationsystem.
onthequalityofmethodologyasfollows:
Recommendation
d I. Good quality patient-oriented evidence.
d Clinicians may find it helpful to use a consistent
d II. Limited quality patient-oriented evidence.
classification/grading scale (encompassing the
d III. Other evidence including consensus guide-
numbers and types of acne lesions as well as
lines, extrapolations from bench research, opin-
diseaseseverity)tofacilitatetherapeuticdecisions
ion, or case studies.
andassessresponsetotreatment.
Clinical recommendations were developed on
the best available evidence tabled in the guidelines DISCUSSION
andexplainedfurtherinthetechnicalreport.These The rating of disease severity is useful for the
arerankedasfollows: initial evaluation and management of acne, to aid
in the selection of appropriate therapeutic agents,
A. Recommendationbasedonconsistentandgood-
andtoevaluateresponsetotreatment.2,3
quality patient-oriented evidence.
Several systems for grading acne exist; most
B. Recommendation based on inconsistent or lim-
employ lesion counting combined with some type
ited quality patient-oriented evidence.
ofglobalassessmentofseverity(eg,mild,moderate,
C. Recommendation based on consensus, opinion,
severe) that represents a synthesis of the number,
or case studies.
size,andextentoflesions.However,thereisnocon-
These guidelines have been developed in accor- sensus on a single or best grading or classification
dancewiththeAmericanAcademyofDermatology/ system.2-15
American Academy of Dermatology Association
‘‘Administrative Regulations for Evidence-Based II. MICROBIOLOGIC AND
ClinicalPracticeGuidelines,’’whichincludetheop- ENDOCRINOLOGIC TESTING
portunityforreviewandcommentbytheentireAAD Microbiologic testing
membership and final review and approval by the Table II shows the recommendations for micro-
AADBoardofDirectors. biologictesting.
Scope Recommendations
These guidelines address the management of d Routinemicrobiologictestingisunnecessaryinthe
adolescent and adult patients presenting with acne evaluationandmanagementofpatientswithacne.
JAMACADDERMATOL Straussetal 653
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Table I. Recommendationsfor agrading Table III. Recommedationsfor endocrinologic
and classification system testing
Strengthof Levelof Strengthof Levelof
Recommendation recommendation evidence References Recommendation recommendation evidence References
Grading/ B II 2-5, 7,11 Endocrinologic testing A I 20,22
classification
system
Table IV. Recommendationsfor topical therapy
Strengthof Levelof
Table II. Recommendationsfor microbiologic Recommendation recommendationevidence References
testing Retinoids A I 25,28,38,41
Benzoyl peroxide A I 42,48,50,51
Strengthof Levelof
Antibiotics A I 52-58,62,65
Recommendation recommendation evidence References
Otheragents A I 70,72,73,75,79
Microbiologic testing B II 16-19
d Thosewhoexhibitacne-likelesionssuggestiveof hormone levels. Presently, there is little evidence
gram-negativefolliculitismaybenefitfrommicro- frompeer-reviewedliteratureindicatingthatroutine
biologic testing. endocrinologictestinghasclinicalvalueintheeval-
uation ofpatientswith acne. Patientswhosehistory
DISCUSSION orphysicalexaminationsuggestshyperandrogenism
Theprevalentbacteriumimplicatedintheclinical may, however, benefit from such testing. In prepu-
courseofacneisPropionibacteriumacnes(Pacnes), bertal children, the signs include acne, early-onset
agram-positiveanaerobethatnormallyinhabitsthe bodyodor,axillaryorpubichair,acceleratedgrowth,
skin and is implicated in the inflammatory phase of advanced bone age, and genital maturation. After
acne. puberty,commonvirilizingsignsandsymptomsare
Gram-negative folliculitis is typically character- infrequentmenses,hirsutism,maleorfemalepattern
ized by pustules and/or nodules most commonly alopecia, infertility, polycystic ovaries, clitoromeg-
located in the perioral and nasal areas. Gram-nega- aly,acanthosisnigricans,andtruncalobesity.20-24In
tivefolliculitisiscausedbyavarietyofbacteria and prepubertal children, a hand film for bone age is a
is unresponsive to conventional antibiotic therapy practical screen prior to specific hormonal testing.
for acne. Bacterial cultures, including antibacterial Increased awareness of clinical signs of androgen
sensitivities, are usually of value in establishing the excess will help identify those patients who may
diagnosisandindeterminingtherapy.16-19 benefitfromfurtherevaluationandtreatmentbyan
endocrinologist or gynecologic endocrinologist. It
Endocrinologic testing is the opinion of the experts that the following
Table III shows the recommendations for endo- laboratory tests may be helpful: free testosterone,
crinologictesting. dehydroepiandrosterone sulfate, leutinizing hor-
mone,andfollicule-stimulatinghormone.
Recommendation
d Routineendocrinologicevaluation(eg,forandro- III. TOPICAL THERAPY
gen excess) is not indicated for the majority of Recommendations for topical therapy are shown
patients with acne. Laboratory evaluation is indi- inTableIV.
cated for patients who have acne and additional
signs of androgen excess. In young children this Recommendations
maybemanifestedbybodyodor,axillaryorpubic d Topical therapy is a standard of care in acne
hair,andclitoromegaly.Adultwomenwithsymp- treatment.
toms of hyperandrogenism may present with re- d Topicalretinoidsareimportantinacnetreatment.
calcitrant or late-onset acne, infrequent menses, d Benzoyl peroxide and combinations with eryth-
hirsutism, male or female pattern alopecia, infer- romycin or clindamycin are effective acne
tility,acanthosisnigricans,andtruncalobesity. treatments.
d Topical antibiotics (eg, erythromycin and clinda-
DISCUSSION mycin) are effective acne treatments. However,
Although androgens play an important role in the use of these agents alone can be associated
thepathogenesisofacne,mostpatientshavenormal with the development of bacterial resistance.
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d Salicylic acid is moderately effective in the treat- or reduces bacterial resistance and enhances effi-
ment of acne. cacy. The combinations are more effective than
d Azelaic acid has been shown to be effective in eitheroftheindividualcomponentsalone.72-75
clinicaltrials,butitsclinicaluse,comparedtoother
agents,haslimitedefficacyaccordingtoexperts. Salicylic acid
d Data from peer-reviewed literature regarding the Salicylicacidhasbeenusedformanyyearsforthe
efficacy of sulfur, resorcinol, sodium sulfaceta- treatmentofacne,althoughfewwell-designedtrials
mide, aluminum chloride, and zinc are limited. ofitssafetyandefficacyexist.Itscomedolyticprop-
d Employing multiple topical agents that affect dif- erties are considered less potent than topical reti-
ferentaspectsofacnepathogenesiscanbeuseful. noids.Itoftenisusedwhenpatientscannottolerate
However,itistheopinionoftheworkgroupthat atopicalretinoidbecauseofskinirritation.76
suchagentsnotbeappliedsimultaneouslyunless
they are known to be compatible. Other topical agents
Azelaic acid has been reported to possess come-
dolytic and antibacterial properties. Data from clin-
DISCUSSION
ical trials indicate that it is effective.77-79 Although
Topical retinoids
sulfurandresorcinolhavebeenusedformanyyears
Theeffectivenessoftopicalretinoidsinthetreat-
in the treatment of acne, evidence from peer-
mentofacneiswelldocumented.25-41Theseagents
reviewed literature supporting their efficacy is lack-
act to reduce obstruction within the follicle and
ing.80 Aluminum chloride possesses antibacterial
therefore are useful in the management of both
activity and, therefore, has been investigated in the
comedonal and inflammatory acne. There is no
treatmentacne.Oftwostudiesinthepeer-reviewed
consensus about the relative efficacy of currently
literature, one found benefit81 and one did not.82
available topical retinoids (tretinoin, adapalene,
Topical zinc alone is ineffective.83-85 There is some
tazarotene, and isotretinoin). The concentration
evidence to suggest efficacy for sodium sulfaceta-
and/orvehicleofanyparticularretinoidmayimpact
mide.86-88
tolerability.33,35 Topical isotretinoin is not currently
availableintheUnitedStates.
IV. SYSTEMIC ANTIBIOTICS
Therecommendations ofsystemicantibioticsare
Benzoyl peroxide
showninTableV.
Benzoyl peroxide is a bactericidal agent that has
proveneffectiveinthetreatmentofacne.Itisavail-
Recommendations
ableinavarietyofconcentrationsandvehicles;how-
d Systemic antibiotics are a standard of care in the
ever, there is insufficient evidence to evaluate and
management of moderate and severe acne and
comparetheefficacyofthesedifferentformulations.
treatment-resistant forms of inflammatory acne.
Ithastheabilitytopreventoreliminatethedevelop-
d Doxycycline and minocycline are more effective
mentofPacnesresistance.42-51Becauseofconcerns
than tetracycline, and there is evidence that min-
of resistance, it is often used in the management of
ocycline is superior to doxycycline in reducing
patientstreatedwithoralortopicalantibiotics.
P acnes.
d Althougherythromyciniseffective,useshouldbe
Topical antibiotics limited to those who cannot use the tetracyclines
Thevalueoftopicalantibioticsinthetreatmentof (ie,pregnantwomenorchildrenunder8yearsof
acne has been investigated in many clinical trials. age because of the potential for damage to the
Both erythromycin52-58 and clindamycin59-66 have skeleton or teeth). The development of bacterial
been demonstrated to be effective and are well resistance is also common during erythromycin
tolerated. Decreased sensitivity of P acnes to these therapy.
antibioticscanlimittheuseofeitherdrugasasingle d Trimethoprim-sulfamethoxazole and trimethoprim
therapeuticagent.58,61 alone are also effective in instances where other
antibiotics cannot be used.
Combinations: Retinoids, benzoyl peroxide, d Bacterial resistance to antibiotics is an increasing
and topical antibiotics problem.
A combination of topical retinoids and topical d The incidence of significant adverse effects with
erythromycin or clindamycin is more effective than antibiotic use is low. However, adverse effect
either agent used alone.67-71 Combining erythromy- profiles may be helpful for each systemic antibi-
cinorclindamycinwithbenzoylperoxideeliminates otic used in the treatment of acne.
JAMACADDERMATOL Straussetal 655
VOLUME56,NUMBER4
Table V.Recommendations for systemic TableVI.Recommendationsforhormonalagents
antibiotics
Strengthof Levelof
Recommendation recommendation evidence References
Strengthof Levelof
Recommendation recommendationevidence References Contraceptive A I 122-125
Tetracyclines A I 90,91,95,121 agents
Macrolides A I 102,108, 111, Spironolactone B II 132
115 Antiandrogens B II 134,135
Trimethoprim- A I 117 Oral B II 137
sulfamethoxazole corticosteroids
DISCUSSION d Oral antiandrogens, such as spironolactone and
Antibioticshavebeenwidelyusedformanyyears cyproterone acetate, can be useful in the treat-
in the management of acne. There is evidence to ment of acne. While flutamide can be effective,
support the use of tetracycline, doxycycline, mino- hepatictoxicitylimitsitsuse.Thereisnoevidence
cycline, erythromycin, trimethoprim-sulfamethoxa- to support the use of finasteride.
zole, trimethoprim, and azithromycin.89-120 Studies d Therearelimiteddatatosupporttheeffectiveness
donotexistfortheuseofampicillin,amoxicillin,or of oral corticosteroids in the treatment of acne.
cephalexin. However, any antibiotic which can re- There is a consensus of expert opinion that oral
duce the P acnes population in vivo and interfere corticosteroid therapy is of temporary benefit in
withtheorganism’sabilitytogenerateinflammatory patients who have severe inflammatory acne.
agents should be effective. It is the opinion of the d In patients who have well-documented adrenal
expert panel that while published data are conflict- hyperandrogenism, low-dose oral corticosteroids
ing,minocyclineanddoxycyclinearemoreeffective may be useful in treatment of acne.
thantetracycline.101,105
A major problem affecting antibiotic therapy of DISCUSSION
acne has been bacterial resistance, which has been Oral contraceptives
increasing.18,121 For this reason, it is the opinion of Thereareclinicaltrialsofestrogen-containingcon-
the work group that patients with less severe traceptive agents for the treatment of acne.122-125
forms of acne should not be treated with oral ThosecurrentlyapprovedbytheUSFoodandDrug
antibiotics, and where possible the duration of Administration (FDA) for the management of acne
such therapy should be limited. Resistance has contain norgestimate with ethinyl estradiol (Ortho
been seen with all antibiotics, but is most common Tri-cyclen; Ortho-MacNeil Pharmaceutical, Inc,
with erythromycin. Raritan, NJ) and norethindrone acetate with ethinyl
The use of oral antibiotics for the treatment of estradiol (Estrostep; Warner Chilcott, Rockaway,
acnemaybeassociatedwithadverseeffects.Vaginal NJ).122-128 There is good evidence and consensus
candidiasis may complicate the use of all oral opinion that other estrogen-containing oral contra-
antibiotics.102,103,107,108 Doxycycline can be associ- ceptives are also equally effective.129,130 The effect
ated with photosensitivity. Minocycline has been onacneofotherestrogen-containingcontraceptives
associated with pigment deposition in the skin, (eg,transdermalpatches,vaginalrings)hasnotbeen
mucous membranes and teeth particularly among studied.
patients receiving long-term therapy and/or higher
doses of the medication. Pigmentation occurs most Spironolactone
often in acne scars, anterior shins, and mucous Spironolactoneisananti-androgenthatexertsits
membranes.Autoimmunehepatitis,asystemiclupus effects by blocking androgen receptors at higher
erythematosus-like syndrome, and serum sickness- doses.131 Dosages of 50 mg to 200 mg have been
likereactionsoccurrarelywithminocycline.102,107 shown to be effective in acne. Spironolactone may
causehyperkalemia,particularlywhenhigherdoses
V. HORMONAL AGENTS are prescribed or when there is cardiac or renal
Hormonal agent recommendations are shown in compromise. It occasionally causes menstrual
TableVI. irregularity.132,133
Recommendations Cyproterone acetate
d Estrogen-containing oral contraceptives can be Cyproterone combined with ethinyl estradiol (in
useful in the treatment of acne in some women. theformofanoralcontraceptive)hasbeenfoundto
656 Straussetal JAMACADDERMATOL
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Table VII. Isotretinoinrecommendations participating in the approved pregnancy preven-
tion and management program (iPLEDGE; see
Strengthof Levelof
below).
Recommendationrecommendationevidence References
Isotretinoin A I 141,148, 150-153, d Mood disorders, depression, suicidal ideation,
155,159, 161 and suicides have been reported in patients tak-
ing this drug. However, a causal relationship has
not been established.
beeffectiveinthetreatmentofacneinfemales.134-136
Higherdoseshavebeenfoundtobemoreeffective DISCUSSION
than lower doses. Cyproterone/estrogen-containing Indications
oral contraceptives are not approved for use in the The approved indication for the use of oral
UnitedStates. isotretinoinhasremainedseverenodulartreatment-
resistant acne since the drug was introduced more
Flutamide than 20 yearsago.However, it isthe opinion ofthe
Flutamide,anon-steroidalantiandrogenapproved expertworkgroupthatthisdrugisalsoindicatedfor
for the management of prostatic hypertrophy or all cases of acne that are either treatment-resistant
cancer and hirsutism, has had some success in the orproducingphysicalorpsychologicalscarring.
managementofacne,butitsuseislimitedbecauseof
thepotentialofhepaticfailure. Dosage
Theapproveddosageis0.5to2.0mg/kg/day.The
drug is usually given over a 20-week course.138-158
Other antiandrogens
Drug absorption is greater when the drug is taken
Finasteride and other compounds with possible
withfood.Theacneexpertworkgroupfeelsstrongly
antiandrogenic effects (eg, cimetidine and ketocon-
thatinitialflaringcanbeminimizedwithabeginning
azole)havenotbeenreportedtobeeffectiveinacne.
dose of 0.5 mg/kg/day or less. Alternatively, lower
dosescanbeusedforlongertimeperiods,withatotal
Oral corticosteroids
cumulativedoseof120to150mg/kg.138Inpatients
Oral corticosteroids may have two modes of
whohaveseverelyinflamedacne,evengreaterinitial
activityinthetreatmentofacne.Onestudydemon-
reduction of dose may be required. In the most
strated that low dose corticosteroids suppress adre-
severecasesofacne,considerationofpre-treatment
nal activity in patients who have proven adrenal
withoralcorticosteroidsmayalsobeappropriate.
hyperactivity.137Expertopinionisthatshort-courses
ofhigherdoseoralcorticosteroidsmaybebeneficial
Adverse effects
inpatientswithhighlyinflammatorydisease.
Isotretinoin,avitaminAderivative,interactswith
many of the biologic systems of the body, and
VI. ISOTRETINOIN consequently has a significant pattern of adverse
Isotretinoin recommendations are shown in effects. The pattern is similar to that seen in hyper-
TableVII. vitaminosis A. Side effects include those of the
mucocutaneous, musculoskeletal, and ophthalmic
Recommendations systems, as well as headaches and central nervous
d Oral isotretinoin is approved for the treatment of system effects. Most of the adverse effects are tem-
severe recalcitrant nodular acne. porary and resolve after the drug is discontin-
d It is the unanimous opinion of the acne work- ued.139,141,143-145,149,152-158
group that oral isotretinoin is also useful for the While hyperostosis, premature epiphyseal clo-
management of lesser degrees of acne that are sure,andbonedemineralizationhavebeenobserved
treatment-resistantorforthemanagementofacne with prolonged use of higher dose retinoids, in the
that is producing either physical or psychological usual course of acne treatment these findings have
scarring. not been identified. Therefore it is the unanimous
d Oralisotretinoinisapotentteratogen.Becauseof opinionoftheacneworkgroupthatroutinescreen-
itsteratogenicityandthepotentialformanyother ingfortheseissuesisnotrequired.Laboratorymon-
adverse effects, this drug should be prescribed itoring during therapy should include triglycerides,
only by those physicians knowledgeable in its cholesterol, transaminase, and complete blood
appropriate administration and monitoring. counts.153,155,157,159
d Female patients of child-bearing potential must Changes in mood, suicidal ideation, and suicide
only be treated with oral isotretinoin if they are have been reported sporadically in patients taking
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Table VIII. Recommendations for miscellaneous Table IX. Recommendations for complementary
therapies therapies
Strengthof Levelof Strengthof Levelof
Recommendation recommendation evidence References Recommendation recommendation evidence References
Intralesional steroids C III 168,169 Herbalagents B II 174-176
Chemicalpeels C III 170-172 Psychological C III 177
Comedoremoval C III 173 approaches
Hypnosis/biofeedback B II 178
isotretinoin. While these events have been seen,
Table X. Recommended dietary restrictions
acausalrelationshiphasnotbeenestablished.None-
theless, there are instances in which withdrawal of Strengthof Levelof
isotretinoin has resulted in improved mood and re- Recommendation recommendation evidence References
introductionofisotretinoinhasresultedinthereturn Effect ofdiet B II 179,180
of mood changes. The symptoms mentioned are
quitecommoninadolescentsandyoungadults,the
DISCUSSION
age range of patients who are likely to receive iso-
Intralesional steroids
tretinoin.Treatmentofsevereacnewithisotretinoin
Intheopinionofexperts,theeffectofintralesional
isoftenassociatedwithmoodimprovement.Thereis
injectionwithcorticosteroidsisawellestablishedand
epidemiologic evidence that the incidence of these
recognizedtreatmentforlargeinflammatorylesions.
events is less in isotretinoin-treated patients than in
Ithasbeenfoundthatpatientsreceivingintralesional
an age-matched general population. There is also
steroidsforthetreatmentofcysticacneimproved.168
evidencethattheriskofdepressedmoodisnogreater
Systemic absorption of steroids may occur. Adrenal
duringisotretinointherapythanduringtherapyofan
suppression was observed in one study.169 The
age-matched acne group treated with conservative
injection of intralesional steroids may be associated
therapy.Nonetheless,patientsmustbemadeaware
with local atrophy. Lowering the concentration
of this possibility and treating physicians should
and/orvolumeofsteroidutilizedmayminimizethese
monitorpatientsforpsychiatricadverseeffects.159-165
complications.
Some patients experience a relapse of acne after
the first course of treatment with isotretinoin. The
Chemical peels
panel feels relapses are more common in younger
Both glycolic acid-based and salicylic acid-
adultsorwhenlowerdosesareused.147-149,151,166,167
based peeling preparations have been used in the
treatmentofacne.Thereisverylittleevidencefrom
iPLEDGE
clinical trials published in the peer-reviewed litera-
Because of the teratogenic effects of isotretinoin
turesupportingtheefficacyofpeelingregimens.170-172
on the fetus, the FDA and the manufacturers have
Further research on the use of peeling in the treat-
approved a new risk management program for
ment of acne needs to be conducted in order to
isotretinoin.154,155 Prescribers, patients, pharmacies,
establishbestpracticesforthismodality.
drug wholesalers, and manufacturers in the United
States are required to register and comply with the
Comedo removal
iPLEDGE program. This program requires manda-
There is limited evidence published in peer-
tory registration of all patients receiving this drug.
reviewed medical literature that addresses the effi-
Detailedinformationcan befoundon theiPLEDGE
cacy of comedo removal for the treatment of acne,
website(www.ipledgeprogram.com).
despiteitslong-standingclinicaluse.173Itis,however,
theopinionoftheworkgroupthatcomedoremoval
VII. MISCELLANEOUS THERAPY
may be helpful in the management of comedones
Recommendations for miscellaneous therapies
resistanttoothertherapies.Also,whileitcannotaffect
areshowninTableVIII.
theclinicalcourseofthedisease,itcanimprovethe
patient’s appearance, which may positively impact
Recommendations
compliancewiththetreatmentprogram.
d Intralesionalcorticosteroidinjectionsareeffective
in the treatment of individual acne nodules.
d Thereislimitedevidenceregardingthebenefitof VIII. COMPLEMENTARY THERAPY
physical modalities including glycolic acid peels Complementary therapy recommendations are
and salicylic acid peels. showninTableIX.
658 Straussetal JAMACADDERMATOL
APRIL2007
Recommendation Classification. Washington, D.C., March 24 and 25, 1990.
d Herbal and alternative therapies have been used JAmAcadDermatol1991;24:495-500.
4. DoshiA,ZaheerA,StillerMJ.Acomparisonofcurrentacne
to treat acne. Although these products appear to
grading systems and proposal of a novel system. Int J
bewelltolerated,verylimiteddataexistregarding
Dermatol1997;36:416-8.
the safety and efficacy of these agents. 5. Allen BS, Smith JG Jr. Various parameters for grading acne
vulgaris.ArchDermatol1982;118:23-5.
6. Lucky AW, Barber BL, Girman CJ, Williams J, Ratterman J,
DISCUSSION Waldstreicher J. A multirater validation study to assess the
Asingleclinicaltrialhasdemonstratedthattopical reliability of acne lesion counting. J Am Acad Dermatol
tea tree oil is effective for the treatment of acne, 1996;35:559-65.
7. CookCH,CentnerRL,MichaelsSE.Anacnegradingmethod
although the onset of action is slower compared
usingphotographicstandards.ArchDermatol1979;115:571-5.
to other topical treatments.174 Other herbal agents,
8. GibsonJR,HarveySG,BarthJ,DarleyCR,ReshadH,BurkeCA.
suchastopicalandoralayurvediccompounds,have Assessinginflammatoryacnevulgaris—correlationbetween
been reported to have value in the treatment of clinical and photographic methods. Br J Dermatol 1984;
acne.175,176 111(suppl27):168-70.
9. BurkeBM,CunliffeWJ.Theassessmentofacnevulgaris—the
Leedstechnique.BrJDermatol1984;111:83-92.
Psychological approaches/hypnosis/
10. Motley RJ, Finlay AY. Practical use of a disability index in
biofeedback theroutinemanagementofacne.ClinExpDermatol1992;17:
The psychological effects of acne may be pro- 1-3.
found,anditistheunanimousopinionoftheexpert 11. Lewis-JonesMS,FinlayAY.TheChildren’sDermatologyLife
Quality Index (CDLQI): initial validation and practical use.
workgroupthateffectiveacnetreatmentcanimprove
BrJDermatol1995;132:942-9.
the emotional outlook of patients. There is weak
12. Martin AR, Lookingbill DP, Botek A, Light J, Thiboutot D,
evidence of the possible benefit of biofeedback- GirmanCJ.Health-relatedqualityoflifeamongpatientswith
assistedrelaxationandcognitiveimagery.177,178 facial acne—assessment of a new acne-specific question-
naire.ClinExpDermatol2001;26:380-5.
13. LasekRJ,ChrenMM.Acnevulgarisandthequalityoflifeof
IX. DIETARY RESTRICTION adultdermatologypatients.ArchDermatol1998;134:454-8.
Recommended dietary restrictions are shown in 14. MallonE,NewtonJN,KlassenA,Stewart-BrownSL,RyanTJ,
Finlay AY. The quality of life in acne: a comparison with
TableX.
general medical conditions using generic questionnaires.
BrJDermatol1999;140:672-6.
Recommendation 15. GuptaMA,JohnsonAM,GuptaAK.Thedevelopmentofan
d Dietary restriction (either specific foods or food AcneQualityofLifescale:reliability,validity,andrelationto
classes)hasnotbeendemonstratedtobeofbenefit subjective acneseverity in mild to moderateacne vulgaris.
ActaDermVenereol1998;78:451-6.
inthetreatmentofacne.
16. Cove JH, Cunliffe WJ, Holland KT. Acne vulgaris: is the
bacterial population size significant? Br J Dermatol 1980;
DISCUSSION 102:277-80.
17. BojarRA,HittelN,CunliffeWJ,HollandKT.Directanalysisof
Therearefewclinicalstudiesavailableinthepeer-
resistance in the cutaneous microflora during treatment of
reviewed literature that directly evaluate the effec-
acnevulgaris withtopical1% nadifloxacinand 2% erythro-
tivenessofdietaryrestrictionortheconsumptionof mycin.Drugs1995;49(suppl2):164-7.
specific foods or food groups to improve acne. 18. Eady EA, Cove JH, Holland KT, Cunliffe WJ. Erythromycin
resistantpropionibacteriainantibiotictreatedacnepatients:
Studiesaddressing the potentialforparticularfoods
associationwiththerapeuticfailure.BrJDermatol1989;121:
to exacerbate acne have been conducted.179,180
51-7.
These studies fail to support a link between the 19. HarkawayKS,McGinleyKJ,FogliaAN,LeeWL,FriedF,Shalita
consumption of chocolate or sugar and acne. Thus, AR,etal.Antibioticresistancepatternsincoagulase-negative
noevidenceexistsontheroleofdietinacne. staphylococci after treatment with topical erythromycin,
benzoyl peroxide, and combination therapy. Br J Dermatol
1992;126:586-90.
REFERENCES 20. Lawrence DM, Katz M, Robinson TW, Newman MC, McGar-
1. EbellMH,SiwekJ,WeissBD,WoolfSH,SusmanJL,Ewigman rigle HH, Shaw M, et al. Reduced sex hormone binding
B, et al. Simplifying the language of evidence to improve globulinandderivedfreetestosteronelevelsinwomenwith
patientcare:Strengthofrecommendationtaxonomy(SORT): severeacne.ClinEndocrinol(Oxf)1981;15:87-91.
apatient-centeredapproachtogradingevidenceinmedical 21. BunkerCB,NewtonJA,KilbornJ,PatelA,ConwayGS,Jacobs
literature.JFamPract2004;53:111-20. HS, et al. Most women with acne have polycystic ovaries.
2. LehmannHP,RobinsonKA,AndrewsJS,HollowayV,Good- BrJDermatol1989;121:675-80.
man SN. Acne therapy: a methodologic review. J Am Acad 22. Lucky AW, Biro FM, Simbartl LA, Morrison JA, Sorg NW.
Dermatol2002;47:231-40. Predictors of severity of acne vulgaris in young adolescent
3. PochiPE,ShalitaAR,StraussJS,WebsterSB,CunliffeWJ,Katz girls:resultsofafive-yearlongitudinalstudy.JPediatr1997;
HI, et al. Report of the Consensus Conference on Acne 130:30-9.
JAMACADDERMATOL Straussetal 659
VOLUME56,NUMBER4
23. Timpatanapong P, Rojanasakul A. Hormonal profiles and of facial acne vulgaris: a randomized trial. Cutis 2001;
prevalence of polycystic ovary syndrome in women with 67(Suppl6):4-9.
acne.JDermatol1997;24:223-9. 41. Lucky AW, Cullen SI, Jarratt MT, Quigley JW. Comparative
24. LuckyAW.Endocrineaspectsofacne.PediatrClinNorthAm efficacy and safety of two 0.025% tretinoin gels: results
1983;30:495-9. from a multicenter double-blind, parallel study. J Am Acad
25. ChristiansenJV,GadborgE,LudvigsenK,MeierCH,Norholm Dermatol1998;38:S17-23.
A,PedersenD,etal.Topicaltretinoin,vitaminAacid(Airol) 42. BelknapBS.Treatmentofacnewith5%benzoylperoxidegel
inacnevulgaris.Acontrolledclinicaltrial.Dermatologica1974; or0.05%retinoicacidcream.Cutis1979;23:856-9.
148:82-9. 43. Bucknall JH, Murdoch PN. Comparison of tretinoin solution
26. BradfordLG,MontesLF.TopicalapplicationofvitaminAacid and benzoyl peroxide lotion in the treatment of acne
inacnevulgaris.SouthMedJ1974;67:683-7. vulgaris.CurrMedResOpin1977;5:266-8.
27. Krishnan G. Comparison of two concentrations of tretinoin 44. Montes LF. Acne vulgaris: treatment with topical benzoyl
solutioninthetopicaltreatmentofacnevulgaris.Practitioner peroxideacetonegel.Cutis1977;19:681-5.
1976;216:106-9. 45. HughesBR,NorrisJF,CunliffeWJ.Adouble-blindevaluation
28. Chalker DK, Lesher JL Jr, Smith JG Jr, Klauda HC, Pochi PE, of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and
Jacoby WS, et al. Efficacy of topical isotretinoin 0.05% placebo in patients with acne. Clin Exp Dermatol 1992;17:
gel in acne vulgaris: results of a multicenter, double- 165-8.
blindinvestigation.JAmAcadDermatol1987;17:251-4. 46. Cunliffe WJ, Dodman B, Ead R. Benzoyl peroxide in acne.
29. ShalitaA,WeissJS,ChalkerDK,EllisCN,GreenspanA,KatzHI, Practitioner1978;220:479-82.
etal.Acomparisonoftheefficacyandsafetyofadapalene 47. Fyrand O, Jakobsen HB. Water-based versus alcohol-based
gel0.1%andtretinoingel0.025%inthetreatmentofacne benzoyl peroxide preparations in the treatment of acne
vulgaris: a multicenter trial. J Am Acad Dermatol 1996;34: vulgaris.Dermatologica1986;172:263-7.
482-5. 48. SchutteH,CunliffeWJ,ForsterRA.Theshort-termeffectsof
30. Clucas A, Verschoore M, Sorba V, Poncet M, Baker M, benzoylperoxidelotionontheresolutionofinflamedacne
Czernielewski J. Adapalene 0.1% gel is better tolerated lesions.BrJDermatol1982;106:91-4.
than tretinoin 0.025% gel in acne patients. J Am Acad 49. YongCC.BenzoylperoxidegeltherapyinacneinSingapore.
Dermatol1997;36:S116-8. IntJDermatol1979;18:485-8.
31. Cunliffe WJ, Caputo R, Dreno B, Forstrom L, Heenen M, 50. SmithEB,PadillaRS,McCabeJM,BeckerLE.Benzoylperoxide
OrfanosCE,etal.Clinicalefficacyandsafetycomparisonof lotion(20percent)inacne.Cutis1980;25:90-2.
adapalene gel and tretinoin gel in the treatment of acne 51. MillsOHJr,KligmanAM,PochiP,ComiteH.Comparing2.5%,
vulgaris: Europe and U.S. multicenter trials. J Am Acad 5%,and10%benzoylperoxideoninflammatoryacnevulgaris.
Dermatol1997;36:S126-34. IntJDermatol1986;25:664-7.
32. DunlapFE,MillsOH,TuleyMR,BakerMD,PlottRT.Adapalene 52. Bernstein JE, Shalita AR. Topically applied erythromycin
0.1% gel for the treatment of acne vulgaris: its superiority ininflammatoryacnevulgaris.JAmAcadDermatol1980;2:
compared to tretinoin 0.025% cream in skin tolerance and 318-21.
patientpreference.BrJDermatol1998;139(suppl52):17-22. 53. JonesEL,CrumleyAF.Topicalerythromycinvsblankvehicle
33. Galvin SA, Gilbert R, Baker M, Guibal F, Tuley MR. Compar- inamulticlinicacnestudy.ArchDermatol1981;117:551-3.
ativetoleranceofadapalene0.1%gelandsixdifferenttreti- 54. PrinceRA,BuschDA,HeplerCD,FeldickHG.Clinicaltrialof
noinformulations.BrJDermatol1998;139(suppl52):34-40. topical erythromycin in inflammatory acne. Drug Intell Clin
34. Grosshans E, Marks R, Mascaro JM, Torras H, Meynadier J, Pharm1981;15:372-6.
AlirezaiM,etal.Evaluationofclinicalefficacyandsafetyof 55. LesherJLJr,ChalkerDK,SmithJGJr,GuentherLC,EllisCN,
adapalene 0.1% gel versus tretinoin 0.025% gel in the Voorhees JJ, et al. An evaluation of a 2% erythromycin
treatment of acne vulgaris, with particular referenceto the ointmentinthetopicaltherapyofacnevulgaris.JAmAcad
onsetofactionandimpactonqualityoflife.BrJDermatol Dermatol1985;12:526-31.
1998;139(suppl52):26-33. 56. PochiPE,BagatellFK,EllisCN,StoughtonRB,WhitmoreCG,
35. Mills OH Jr, Berger RS. Irritation potential of a new topical Saatjian GD, et al. Erythromycin 2 percent gel in the treat-
tretinoinformulationandacommercially-availabletretinoin mentofacnevulgaris.Cutis1988;41:132-6.
formulationasmeasuredbypatchtestinginhumansubjects. 57. Dobson RL, Belknap BS. Topical erythromycin solution in
JAmAcadDermatol1998;38:S11-6. acne. Results of a multiclinic trial. J Am Acad Dermatol
36. IoannidesD,RigopoulosD,KatsambasA.Topicaladapalene 1980;3:478-82.
gel0.1%vs.isotretinoingel0.05%inthetreatmentofacne 58. Mills O Jr, Thornsberry C, CardinCW, Smiles KA, Leyden JJ.
vulgaris:arandomizedopen-labelclinicaltrial.BrJDermatol Bacterial resistance and therapeutic outcome following
2002;147:523-7. three months of topical acne therapy with 2% erythro-
37. Kakita L. Tazarotene versus tretinoin or adapalene in the mycin gel versus its vehicle. Acta Derm Venereol 2002;
treatmentofacnevulgaris.JAmAcadDermatol2000;43:S51-4. 82:260-5.
38. ShalitaAR,ChalkerDK,GriffithRF,HerbertAA,HickmanJG, 59. Padilla RS, McCabe JM, Becker LE. Topical tetracycline
MaloneyJM,etal.Tazarotenegelissafeandeffectiveinthe hydrochloride vs. topical clindamycin phosphate in the
treatment of acne vulgaris: a multicenter, double-blind, treatment of acne: a comparative study. Int J Dermatol
vehicle-controlledstudy.Cutis1999;63:349-54. 1981;20:445-8.
39. Ellis CN, Millikan LE, Smith EB, Chalker DM, Swinyer LJ, 60. Thomas DR, Raimer S, Smith EB. Comparison of topical
Katz IH, et al. Comparisonofadapalene0.1%solutionand erythromycin1.5percentsolutionversustopicalclindamycin
tretinoin0.025%gelinthetopicaltreatmentofacnevulgaris. phosphate 1.0 percent solution in the treatment of acne
BrJDermatol1998;139(suppl52):41-7. vulgaris.Cutis1982;29:624-5,628-32.
40. WebsterGF,BersonD,SteinLF,FivensonDP,TanghettiEA, 61. Shalita AR, Smith EB, Bauer E. Topical erythromycin vs
LingM.Efficacyandtolerabilityofonce-dailytazarotene0.1% clindamycin therapy for acne. A multicenter, double-blind
gel versusonce-dailytretinoin 0.025%gel inthe treatment comparison.ArchDermatol1984;120:351-5.
660 Straussetal JAMACADDERMATOL
APRIL2007
62. LeydenJJ,ShalitaAR,SaatjianGD,SeftonJ.Erythromycin2% 78. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20%
gelincomparisonwithclindamycinphosphate1%solution azelaic acid cream in the treatment of acne vulgaris. Com-
inacnevulgaris.JAmAcadDermatol1987;16:822-7. parison with vehicle and topical tretinoin. Acta Derm
63. McKenzie MW, Beck DC, Popovich NG. Topical clindamycin VenereolSuppl(Stockh)1989;143:35-9.
formulationsfor the treatmentof acnevulgaris.An evalua- 79. Hjorth N, GraupeK. Azelaicacid for the treatmentof acne.
tion.ArchDermatol1981;117:630-4. A clinical comparison with oral tetracycline. Acta Derm
64. KuhlmanDS,CallenJP.Acomparisonofclindamycinphos- VenereolSuppl(Stockh)1989;143:45-8.
phate1percenttopicallotionandplacebointhetreatment 80. ElsteinW.Topicaldeodorizedpolysulfides.Broadscopeacne
ofacnevulgaris.Cutis1986;38:203-6. therapy.Cutis1981;28:468-72.
65. Becker LE, Bergstresser PR, Whiting DA, Clendenning WE, 81. Hurley HJ, Shelley WB. Special topical approach to the
DobsonRL,JordanWP,etal.Topicalclindamycintherapyfor treatment of acne. Suppression of sweating with alumi-
acne vulgaris. A cooperative clinical study. Arch Dermatol num chloride in an anhydrous formulation. Cutis 1978;22:
1981;117:482-5. 696-703.
66. Ellis CN, Gammon WR, Stone DZ, Heezen-Wehner JL. 82. Hjorth N, Storm D, Dela K. Topical anhydrous aluminum
A comparison of Cleocin T Solution, Cleocin T Gel, and chloride formulation in the treatment of acne vulgaris:
placebo in the treatment of acne vulgaris. Cutis 1988;42: adouble-blindstudy.Cutis1985;35:499-500.
245-7. 83. CochranRJ,TuckerSB,FlanniganSA.Topicalzinctherapyfor
67. Glass D, Boorman GC, Stables GI, Cunliffe WJ, Goode K. acnevulgaris.IntJDermatol1985;24:188-90.
Aplacebo-controlledclinicaltrialtocompareagelcontaining 84. StainforthJ,MacDonald-HullS,Papworth-SmithJW,EadyEA.
acombinationofisotretinoin(0.05%)anderythromycin(2%) Asingle-blindcomparisonoftopicalerythromycin/zinclotion
with gels containing isotretinoin (0.05%) or erythromycin and oral minocycline in the treatment of acne vulgaris.
(2%)aloneinthetopicaltreatmentofacnevulgaris.Derma- JDermatologTreat1993;4:119-22.
tology1999;199:242-7. 85. Bojar RA, Eady EA, Jones CE, Cunliffe WJ, Holland KT.
68. Mills OH Jr, Kligman AM. Treatment of acne vulgaris with Inhibitionoferythromycin-resistantpropionibacteriaonthe
topically applied erythromycin and tretinoin. Acta Derm skin of acne patients by topical erythromycin with and
Venereol1978;58:555-7. withoutzinc.BrJDermatol1994;130:329-36.
69. RichterJR, BousemaMT,De BoulleKLV,Degreef HJ,PoliF. 86. ThiboutotD.Newtreatmentsandtherapeuticstrategiesfor
Efficacy of a fixed clindamycin phosphate 1.2%, tretinoin acne.ArchFamMed2000;9:179-87.
0.025%gelformulation(Velac)inthetopicalcontroloffacial 87. LebrunCM.Rosaccreamwithsunscreens(sodiumsulfacet-
acnelesions.JDermatologTreat1998;9:81-90. amide10%andsulfur5%).Skinmed2004;3:92.
70. ZouboulisCC,DerumeauxL,DecroixJ,Maciejewska-Udziela 88. Tarimci N, Sener S, Kilinc T. Topical sodium sulfacetamide/
B, Cambazard F, Stuhlert A. A multicentre, single-blind, sulfurlotion.JClinPharmTher1997;22:301.
randomized comparison of a fixed clindamycin phosphate/ 89. Lane P, Williamson DM. Treatment of acne vulgaris with
tretinoin gel formulation (Velac) applied once daily and a tetracyclinehydrochloride:adouble-blindtrialwith51patients.
clindamycinlotionformulation(DalacinT)appliedtwicedaily BrMedJ1969;2:76-9.
inthetopicaltreatmentofacnevulgaris.BrJDermatol2000; 90. Smith JG Jr, Chalker DK, Wehr RF. The effectiveness of
143:498-505. topicalandoraltetracyclineforacne.SouthMedJ1976;69:
71. Rietschel RL, Duncan SH. Clindamycin phosphate used in 695-7.
combination with tretinoin in the treatment of acne. Int 91. Gratton D, Raymond GP, Guertin-Larochelle S, Maddin SW,
JDermatol1983;22:41-3. Leneck CM, Warner J, et al. Topical clindamycin versus
72. ChalkerDK,ShalitaA,SmithJGJr,SwannRW.Adouble-blind systemic tetracycline in the treatment of acne. Results of a
study of the effectiveness of a 3% erythromycin and 5% multiclinictrial.JAmAcadDermatol1982;7:50-3.
benzoyl peroxide combination in the treatment of acne 92. Katsambas A, Towarky AA, Stratigos J. Topical clindamycin
vulgaris.JAmAcadDermatol1983;9:933-6. phosphatecomparedwithoraltetracyclineinthetreatment
73. TschenEH,KatzHI,JonesTM,MonroeEW,KrausSJ,Connolly ofacnevulgaris.BrJDermatol1987;116:387-91.
MA,etal.Acombinationbenzoylperoxideandclindamycin 93. Braathen LR. Topical clindamycin versus oral tetracycline
topical gel compared with benzoyl peroxide, clindamycin andplaceboinacnevulgaris.ScandJInfectDisSuppl1984;
phosphate, and vehicle in the treatment of acne vulgaris. 43:71-5.
Cutis2001;67:165-9. 94. Anderson RL, Cook CH, Smith DE. The effect of oral and
74. Leyden JJ, Hickman JG, Jarratt MT, Stewart DM, Levy SF. topical tetracycline on acne severity and on surface lipid
Theefficacyandsafetyofacombinationbenzoylperoxide/ composition.JInvestDermatol1976;66:172-7.
clindamycin topical gel compared with benzoyl peroxide 95. Blaney DJ, Cook CH. Topical use of tetracycline in the
alone and a benzoyl peroxide/erythromycin combination treatment of acne: a double-blind study comparing topical
product.JCutanMedSurg2001;5:37-42. and oral tetracycline therapy and placebo. Arch Dermatol
75. LookingbillDP,ChalkerDK,LindholmJS,KatzHI,KempersSE, 1976;112:971-3.
Huerter CJ, et al. Treatment of acne with a combination 96. Rapaport M, Puhvel SM, Reisner RM. Evaluation of topical
clindamycin/benzoylperoxidegelcomparedwithclindamy- erythromycin and oral tetracycline in acne vulgaris. Cutis
cin gel, benzoyl peroxide gel and vehicle gel: combined 1982;30:122-6,130,132-5.
results of two double-blind investigations. J Am Acad 97. NorrisJF,HughesBR,BaseyAJ,CunliffeWJ.Acomparisonof
Dermatol1997;37:590-5. the effectiveness of topical tetracycline, benzoyl-peroxide
76. Shalita AR. Treatment of mild and moderate acne vulgaris gel and oral oxytetracycline in the treatment of acne. Clin
with salicylic acid in an alcohol-detergent vehicle. Cutis ExpDermatol1991;16:31-3.
1981;28:556-8,561. 98. SauerGC.Safetyoflong-termtetracyclinetherapyforacne.
77. Cunliffe WJ, Holland KT. Clinical and laboratory studies on ArchDermatol1976;112:1603-5.
treatmentwith20%azelaicacidcreamforacne.ActaDerm 99. Baer RL, Leshaw SM, Shalita AR. High-dose tetracycline
VenereolSuppl(Stockh)1989;143:31-4. therapyinsevereacne.ArchDermatol1976;112:479-81.