2011 - 2012 Annual Evidence Update on Acne vulgaris Introduction Welcometothe sixth Annual Evidence Updateon Acne Vulgaris from the Centreof Evidence-Based Dermatologyat theUniversityof Nottingham where we search for newUK national guidelines andsystematicreviews of randomised controlledtrialspublished or indexed since the last Annual Evidence Update in February2011. Inaddition tocollating newresources, we also include a "what'snew" analysis, discussing the newevidence and its implicationsfor clinical practice. Thisupdate isaimed at healthcare professionals, but we also hope that manypeople who have acne will find at least someof the information interesting. Weusesystematicreviews as our core evidencesourcefor Annual Evidence Updates because of the well-known hazards in interpreting theresults of singleresearch studies, the resultsof which tend tobe contradictedwith time. (TVPereiraet al). If you want to delve moredeeplyinto thetopic areas, we recommendthat you readthe original articles and come to your own decisions about their utility. In previous years, our annual evidence updates were produced incollaboration with NHS Evidence-skin disorders, managedbythe National Instituteof Health andClinical Excellence (NICE). However, NICEhave decided to reorganise thespecialist libraries which has meant that NHS Evidence-skindisordersand itsannualevidence updates no longer exist.Whilst one of us(HW) continues towork with NICE as its expert advisor for NHS Evidence https://www.evidence.nhs.uk/nhs-evidence-content/medicines-information (accessed August 12th 2013), we have takenthe decision at our Centre of Evidence-Based Dermatologytotryand continue our updates onacne and eczemaunder our own steam based onthefantasticfeedback we have hadfrom you, our readers. 2011 – 2012 Annual Evidence Update on Acne Vulgaris – Results A literature searchwas carried out to identify new guidelinesand systematicreviews relating toacnevulgaris(common acne) that have been published or indexed since the 2011 Annual Evidence Update on AcneVulgaris.Theresult of this search isthe 2012 Annual Evidence Update on Acne Vulgaris. Search period January2010 was set asthelimit for earliest publication dateinthis year'ssearches, to allowfor anydelays in indexing of citationsin thebibliographic databasesused (which might meanthe citationswere not found inthesearchesfor the previous Annual Evidence Update in February2011). All the searches were carried out for thelast timeon 22nd August, 2012. Sources Searched Thefollowing sourceswere searched: Ovid MEDLINE (using SIGN MEDLINE systematic reviewfilter) Ovid EMBASE (using SIGN EMBASE systematic reviewfilter) PubMed (using PubMed Clinical Queries systematic reviewfilter) Cochrane Library NHS Evidence – www.evidence.nhs.uk All citationsfoundinthesearcheswere hand searched byreading thetitles and abstractsto identifyguidelines and potential systematicreviews relevant to acnevulgaris. For all 1 potential systematicreviews where therewas still somedoubt, thefulltexts were thenread to ensurethat theywereindeed systematicreviews. Thedefinition of asystematicreviewfrom theGlossaryof CochraneCollaborationTerms on the Cochrane Collaboration website was used: A reviewof aclearlyformulatedquestionthat uses systematic andexplicit methodsto identify, select, andcriticallyappraise relevant research, andtocollect andanalyse data from the studiesthat areincluded in thereview. Statistical methods(meta-analysis) mayor maynot beusedtoanalyse and summarisetheresults of the included studies. RESULTS Newguidelines and citationsfor newsystematicreviews judgedof direct relevance to the topic of acnevulgaris and itstreatment arelistedbelow. Linksto PubMed abstractsorfree full text, where available, areprovided. Please notethat theinclusionof citationsinthislist doesnot implyendorsement. We not accept responsibilityfor the content or qualityof includedstudies. A large number of citations were identified aspossible systematicreviews for theAnnual Evidence Update in theinitial searchresults, butwere subsequentlyexcluded onthe grounds of alack of aclear systematicreviewmethodologyor for other reasons. These citations are listedat theend of thispage under the heading "Excluded references". ________________________________________________________________________ European Guideline Nast A, DrénoB, Bettoli V, DegitzK, Erdmann R, FinlayAY, Ganceviciene R, Haedersdal M, Layton A, López-EstebaranzJL, Ochsendorf F, Oprica C, Rosumeck S, RzanyB, Sammain A, SimonartT, Veien NK, Zivković MV, Zouboulis CC, Gollnick H; European Dermatology Forum. European evidence-based (S3)guidelines for the treatment of acne. J Eur Acad Dermatol Venereol. 2012Feb;26Suppl 1:1-29. Link to PubMed abstract Systematic Reviews Zhao YE, HuL,WuLP,Ma JX. A meta-analysis of association between acne vulgaris and Demodexinfestation. Journal of Zhejiang UniversitySCIENCE B. 13(3):192-202, 2012Mar. Link to PubMed abstract Note: MEDLINE andWeb of knowledge searched 2 VeithWB, Silverberg NB. Theassociation of acnevulgaris with diet. Cutis. 88(2):84-91, 2011Aug. Link to PubMed abstract Note: PubMedonly searched. Dunn LK, O’Neill JL, Feldman SR. Acne in adolescents:qualityof life, self-esteem,mood andpsychologicaldisorders. DermatologyOnline Journal. 17(1):1, 2011. Link to PubMed abstract Note: Medline only searched AlharithyR. Adolescent’s acne: scarring inside out! Journal of theSaudi Societyof Dermatology&DermatologicSurgery(2011) 15, 43–46. Link to abstract Note: Medline, PsychINFO, EMBASE and CINHAL searched. Crijns HJ, StrausSM, Gispen-deWiedC, de Jong-van denBerg LT. Compliance with pregnancyprevention programmes of isotretinoin in Europe: asystematic review British Journal of Dermatology. 164(2):238-44, 2011 Feb. Link to PubMed abstract Note: Medline and EMBASE searched Shapiro S, Heremans A, Mays DA, Martin AL, Hernandez-Medina M, Lanes S. Use of topicaltretinoin and thedevelopment of noncutaneousadverse events: evidence from asystematicreview of theliterature J Am Acad Dermatol. 2011 Dec;65(6):1194-201. Link to pubmedabstract 3 Note: Medline, embaseand Current Contentsfor relevant studies of anydesign including case reports searched Siedler EMand Kimball AB. Meta-analysis of randomised controlled trials using 5% benzoyl peroxide and clindamycin versus 2.5% benzoyl peroxide and clindamycin topical treatments inacne. Journal of theAmericanAcademyof Dermatology. 65(4):e117-9, 2011Oct. Link to PubMed abstract Note:L PubMedand FDA summariessearched. Brandsetter AJ andMaibach HI. Topical dosejustification: benzoyl peroxide concentrations. J Dermatolog Treat. 2011 Dec 27. Link to PubMed abstract Note: PubMed, Embaseand a sciencecitation indexweresearched. Mohd Nor NH and AzizZ. A systematic reviewof benzoyl peroxide for acnevulgaris. J Dermatolog Treat. 2012 July25 Link to PubMed abstract Note: Cochrane library,Medline, EBSCohost and PubMed, CINAHL andScience directwas searched. GambleR, DunnJ, Dawson A, Petersen B, McLaughlin L, Small A, KindleS, Dellavalle RP. Topical antimicrobial treatment of acne vulgaris: an evidence-based review. Am JClin Dermatol. 2012 Jun 1;13(3):141-52. Link to PubMed abstract Note: Ovid, MEDLINE, EMBASE and Cochrane librarysearched. Webster GF. Evidence-based review: fixed-combinationtherapyand topical retinoids inthetreatment of acne. 4 J DrugsDermatol. 2011Jun;10(6):636-44 Link to PubMed abstract Note: PubMedonly searched. PurdyS and deBerker D. Acne vulgaris. Clinical evidence, 2011. Link to PubMed abstract Note: MEDLINE, EMBASE, theCochranedatabase of systematicreviews, the USfoodand drug administration (FDA) alerts andtheMedicines and healthcareproducts regulatory agency (MRHA) were searched. Ong MW and Bashir SJ. Fractional laser resurfacingfor acnescars: areview. British Journal of Dermatology. 166(6):1160-9, 2012 Jun. Link to PubMed abstract Note: PubMedand Scopus searched. Dreno B, FischerTC, Perosino E, Poli F, VieraMS, Rendon MI, BersonDS, Cohen JL, RobertsWE, StarkerI,Wang B. Expert opinion: efficacyof superficial chemical peels in active acnemanagement – what can we learnfrom the literaturetoday? Evidence-based recommendations. Link to PubMed abstract Note: PubMedonly searched. Brown J, Farquhar C, Lee O, Toomath R, JepsonRG. Spironolactone versus placebo or in combinationwith steroidsfor hirsuitsm/acne. Cochrane Link to Cochrane abstract Garner SE, EadyA, Bennett C, Newton JN, Thomas K, PopescuCM. Minocycline for acnevulgaris: efficacyandsafety. Cochrane Link to Cochrane abstract 5 Arowojolu AO, Gallo MF, LopezLM, Grimes DA Combined oral contraceptive pills for treatment of acne. Cochrane Link to Cochrane abstract Excluded references Zeichner JA Optimizing topical combination therapyfor thetreatment of acne vulgaris J DrugsDermatol. 2012Mar;11(3):313-7 Link to pubmedabstract Note: Nomethodssection and nodetails of systematicsearchstrategy Gold MH Photodynamic therapy Curr Probl Dermatol. 2011;42:181-92 Link to pubmedabstract Note: Nodetailedmethods sections andno systematicsearch strategy Szczepaniak D,Treadwell P. AcneTherapyin primarycare: Comprehensive reviewof current evidencebased interventions andtreatments. Adolesc Med State Art Rev. 2011 Apr;22(1):77-96.Link toPubMed abstract Note: Nosystematic search andincompletemethodology reporting. Gannon M, Underhill M, Wellik KE. Clinical enquiries.Whichoral antibiotics are best for acne? J. Fam. Pract. 2011May;60(5):290-2 Link tofull text Note: Noclear method described andno systematic search strategy 6 Feldman SR,Tan J, Poulin Y, DirschkaT, Kerrouche N, Manna V. Theefficacyof adapalene-benzoyl peroxide combination increaseswith number of acne lesions. J Am Acad Dermatol. 2011 Jun;64(6):1085-91. Link to pubmedabstract Note: Nosearch strategy, sounclear howthe 3pooled trials wereidentified andthereforeat risk of publication bias. Gold MH Clindamycin Phosphate 1.2% and Benzoyl Peroxide 2.5% Gelfor theTreatment of Moderate to severe Acne: An update TheJournal of Clinical &Aesthetic Deramtology. 5(1):30-5, 2012Jan Link to pubmedabstract Note: nomethodologyand no searchstrategy Williams HC, Dellavalle RP, Garner S. Acne vulgaris Lancet. 2012Jan 28;279(9813):361-72 Link to pubmedabstract Note: systematic searching however themethodsof synthesising evidence was not explicit. Woolery-Lloyd H, VieraMH, ValinsW. Laser therapyin black skin. Facial Plastic SurgeryClinics of NorthAmerica. 19(2):405-16, 2011May Link to pubmedabstract Note: Noclear methodology Pierard-Franchimont C,Paquet P, PierardGE Newapproaches in light/laser therapies andphotodynamic treatment of acne Expert Opin Pharmacother. 2011 Mar; 12(4):493-501 Link to pubmedabstract Note: Noclear method outlined 7 Comin AF, de Albuquerque SantosZE Relationship between diet’sglycemic load andacne. <Relacao entrecargaglicemica da dieta e acne.> Scientia Medica. 21(1) (pp37-43), 2011. Link tofull text Note: Nomethodology and no details of search inmaintext Leyden JJ, Del RossoJQ Oral Antibiotic therapyfor AcneVulgaris. Pharmacokinetic and Pharmacodynamic perspectives. J Clin Aesthet Dermatol. 2011 February; 4(2):40-47 Link to pubmedabstract Note: Noclear method or systematic search Arora MK, YadavA, SaniV. Role of hormonesin acne vulgaris. Clinical Biochemistry. 44(13):1035-40, 2011Sep. Link to PubMed abstract Note: Nooutline of methodology and nosystematic searchstrategy. 8 2012 Annual Evidence Update on Acne Vulgaris –Commentary "What's new?" — atour of the2012 Annual Evidence Updateon Acne Vulgariswith the busyclinicianinmind Dr KetakiBhate, Academic Clinical Fellow in Dermatology, NottinghamUniversity Hospitals NHS Trust, andProfessor HywelWilliams, Director of the Centreof Evidence-Based Dermatology at theUniversityof Nottingham . What this guideis all about Our task inthis commentary is toreadthrough allthe newguidelines andsystematicreview evidence we have foundin the Results section inorder toprovide you with a summaryof important developmentsin acne researchthat might changeyour practice — either by stopping something ineffective or harmful, or encouraging you to adopt anewtreatment approachthatmight bebeneficial. Sometimestheevidence will just reinforce what you do already, which can alsobe useful if, likeus, youare worriedthat you might bemissing something newand important.Wealso highlight somemethodological issues in the published studies.Wehope that youfindsomeof these insightsinteresting, educational and useful. Inthe 2011 Annual Evidence Updateon AcneVulgaris (link), wefoundtwoguidelines and five articlesthatfall within our definition of asystematicreview. Thequalityof those systematicreviews was rather disappointing, withonly one out of thefivereviews searching morethanone electronicdatabase. Thecurrent 2012 updateincluded oneguideline and 17 systematicreviews. You will see that we have excluded lots of articlesthatwere initially pickedup aspossible systematicreviews byour searches, inmost casesdue toan absence of details of anysystematic reviewmethodologyin thefull articles. Guidelines European evidencebased (S3) guidelines for thetreatment of acne One newguideline was found in our search in 2011 to2012: aguideline in acne composed bynominated experts from the European DermatologyForum andThe European Academy of Dermatologyand Venereology working in theacnefield. It isthefirst of itskindstemming from Europe. Most well known acne therapieswere discussed including topical, systemic and light basedtherapies andthesetherapies were divided into treatmentsfor comedonal acne, papulopustular acne and nodular/conglobate acne. Overall, after reviewing theclinical trialsfound intheir searches theauthors recommended atopical retinoidfor comedonal acne (but this was not astrong recommendation), adapalene or clindamycin in combination with benzoyl peroxide topicallyfor mild to moderate papulopustular acneand isotretinoin orallyfor severe papular-pustular acne, moderatenodular acne or severe nodular/conglobateacne. Systemic antibioticswere not recommendedfor comedonal acne and were not strong recommendations for papulopustular or nodular/conglobate acne. Hormonaltherapies were recommended as an alternative for female patients with papulopustular/nodular/conglobateacne. Theseguidelines highlight thelack of evidencefor light based or laser therapies at present particularly with regardto side effect profiles. 9 Search criteriawere thoroughand recommendations were agreedin aconsensus bya panel of experts, andthe strength of recommendationstook intoconsiderationthe level of evidence the recommendations stemmedfrom; overall making this asturdyguideline which can berelied upon. Over 300referenceswere included. The onlyaspect that let down this otherwise thoroughguideline was that potential conflicts of interest of theauthorswere not declared, andseveral areknown to work for theindustry. Oftenacnetherapybegins in primarycare bygeneralpractitioners and theintroduction of theseguidelines will be useful particularlytothoseGPs initiating therapy but also to practising dermatologists dealing with moresevereforms of acne. They are valid until2015 at which point theyare due tobe updated. Systematicreviews Acne vulgaris andDemodex infestation Demodexmitesarecolonisers of human skinfound onthe nose, cheeks, forehead, temples, chin, external ear, scalp and upper chest andprincipally reside aroundsebaceous glands. Themitehasbeen associated with several otherskinconditions such asrosacea. The authorsof thismeta-analysis set aboutto collateevidence from case-control studiesto confirmthe link between demodexinfestation andacne vulgaris. Their search strategydated back to1950and involved 2 English databases –MEDLINE and Institute of scientific informationWeb of Knowledge andone Chinesedatabase – China National Knowledge infrastructure. Thestudyemployed definitive inclusion and exclusion criteria which allowed them toisolate studies which would be included into ameta-analysis. All in all, 60 Chinese and just 3 English papers were included in the analysis. A χ2 test was applied to all papers with 43 of themfinding an association and15, with no association.The pooled odds ratio (OR) of an associationbetween demodexinfestation and thedevelopment of acne was significant at 2.80(95%CI 2.34-3.36). Fail safe numberformulaewere applied to reduce publication bias –this number was 18,477meaning that many papers with negative conclusions would be requiredbeforetheconclusion that demodexand acne were related could be doubted. The authors presented dataappropriatelyinforest plotsallowing easy readability and concluded that acnevulgarisis significantlyrelatedto Demodexinfestation but not asclosely as therelationship between demodexand rosacea.Overall this isa thorough systematicreview which indicates surprisinglylargeliteratureondemodexand acnefrom China. Themain drawback of thereviewis that thereistoomuch emphasison quantitative meta-analysis without enoughconsideration of therisk of biasassociatedwith the observational studiesfound. Intermsof affecting our practice however, thesefindings are unlikelyto influenceour clinical work otherthan letting our patientsknowdemodexmay be implicatedshould theyask. Thestudiestodate cannot separatecausefrom effect. If causal, it is unclear whether it isthe demodexordemodex-associatedbacteria at this stage. This study highlightstheneedfor further studieslooking intomanipulatingdemodexspecies as atherapeutictarget. Diet and acne Thetopic of diet andacne has becomequitecontroversial with an influxof newstudies and hypotheses over thelast10 years. Theauthorsof this article aimedtosystematically 10
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