ISSN 0001-5555 ActaDV Volume 100 2020 Supplement No. 220

Advances in Dermatology and Venereology

A Non-profit International Journal for Interdisciplinary Skin Research, Clinical and Experimental Dermatology and Sexually Transmitted Diseases

ABSTRACTS from EB2020 1st World Congress on Epidermolysis Bullosa January 19–23, 2020 Official Journal of - European Society for Dermatology and London, UK Psychiatry

Affiliated with - The International Forum for the Study of Itch

Immediate Open Access

Acta Dermato-Venereologica

www.medicaljournals.se/adv

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Journal Compilation ©2020ActaDermato-Venereologica. www.medicaljournals.se/acta Abstracts from EB20201 Epidermolysis Bullosa January 19–23,2020 London, UK st World Congress on Acta DermVenereol 2020;Suppl 220:1–82 doi: 10.2340/00015555-3586

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Author index(posters) Speakerindex Author index Poster Abstracts (P) Orallectureabstracts(OP) Abstracts Programme Contents ofthis Abstract Book Organising Committee Scientific Committee Martin Laimer Mark Koh Alain Hovnanian Ravi Hiremagalore Cristina Has Ignacia Fuentes Jo-David Fine Anja Diem Hana Buckova Leena Bruckner-Tuderman Anna Bruckner Marieke Bolling Johann Bauer Research Director, DEBRA UK Caroline Collins Austria Singapore France India Germany Chile USA Austria Czech Republic Germany USA Netherlands Austria 1 st World Congress onEpidermolysisBullosa Giovanna Zambruno Jakub Tolar Katsuto Tamai Eli Sprecher Andrew South Agnes Schwieger-Briel Francis Palisson Hagen Ott Dedee Murrell John McGrath Anna Martinez Peter Marinkovich Thomas JeffersonUniversity, Abstracts from the Philadelphia, USA 29–81 5–28 2–4 Jouni Uitto 82 82 EB2020 1 Italy USA Japan Israel USA Switzerland Chile Germany Australia UK UK USA

st WorldCongressonEpidermolysisBullosa Guy’s &St.Thomas’ NHSFoundation St John’s InstituteofDermatology Trust, London,UK Jemima Mellerio Acta DermVenereol Suppl220 1 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Monday 20 Jouni UittoandJemimaMellerio 8.30 OpeningoftheCongress Monday 20 PROGRAMME 2 Tuesday 21 4.20–4.55 3.40–4.20 1.25–3.10 11.05–12.25 10.00–11.05 8.55 –9.30 8.40 –8.55 8.35 –8.40 8.40–10.25 8.30–8.40 Subhanitthaya Chottianchaiwat: Vicki Chen: Form ofEpidermolysisBullosaSimplex:NaxosDisease(P137) Hannah Mumber:BiallelicJUP MutationinFamilieswith Arrhythmogenic Right Ventricular CardiomyopathyandSkinFragilityinthe dystrophic epidermolysisbullosa(P34) Christina Guttmann-Gruber: The impactoflow-dosecalcipotriol ointmentonwoundhealing,pruritusandpaininpatientswith EB2020 1 th th st Understanding oculardiseaseintheDEBmousemodel:challenges ofasymmetryandsurvival(P107) January, 2020-Plenary January2020-Plenary January2020–Oralposterstationpresentations Anna Bruckner:TheEBclinicalcharacterizationandoutcomesdatabase(OP21) Jemima Mellerio: Natural history–implicationsfor clinicaltrialdesign,Chair: JouniUitto Dedee Murrell: Topical treatments –anupdate(OP19) David Woodley: Thomas Magin:EBStarget andtreatmentoptions/targeting EBasaninflammatorydisease(OP17) Therapeutics, Chair:JouniUitto arising inrecessivedystrophicepidermolysisbullosa(P128) Jasbani Dayal:Heterogeneousaddictionto TGFβ signallinginlifethreateningcutaneoussquamouscellcarcinomas recessive dystrophicepidermolysisbullosa:aprospectivestudy(P73) Angela Filoni: Oral poster presentations Jemima Mellerio: internal) (OP15) Leena Bruckner-Tuderman: InterdisciplinarymanagementandtherapiesforEBassociatedcancers(skin,mucosal, Andy South: Kevin Harrington:KEYNOTE:Precision medicinefor SCC(OP13) Cancer &cancer therapeutics,Chair:JohannBauer Liat Samuelov: epidermolysis bullosa(P112) Esteban Chacon-Solano: Oral poster presentations Giovanna Zambruno:miRNA inDEB(OP12) Dimitra Kiritsi:LosartanforRDEBtrial–resultsandinternationalperspectives(OP11) Alexander Nyström: Inflammation, fibrosis&therapeutics,Chair:LeenaBruckner-Tuderman David Abraham:Learningsfromotherdiseases(cellinflammation)(OP9) Maria JoseEscamez:Clinicalresearch(OP8) Josefine Hirschfeld: Sabine Eming: The challengesofEBskin.Chair:Peter Marinkovich John McGrath:Curativevsdiseasemodifyingstrategies(OP5) Leena Bruckner-Tuderman: ModellingEBintheresearchenvironment(OP4) Johann Bauer:EBasasystemicdisease–implicationsforresearch(OP3) Current dilemmas–adebate The complexityofEB.Chair:Jo-David Fine Cristina Has:EBclassificationandupdatesfromthe2019meeting(OP2) Jouni Uitto: dystrophic epidermolysisbullosa (P7) Martin Barbier:Self-assembledskinsubstitutes and retroviralgenetherapyforthepermanenttreatmentofrecessive CRISPR/Cas9 RiboNucleoProtein complexes(P115) Joanna Jackow: Oral poster presentations Dennis Roop:StateoftheartiPSCs(OP26) Katsuto Tamai: HMGB1peptide(OP25) Su Lwin:Fibroblastgenetherapy(OP24) Jakub Tolar: Combiningapproaches–BMT &systemic treatment(OP23) Cell manipulationandtherapies:Chair:JohnMcGrath Jemima Mellerio: st WorldCongressonEpidermolysisBullosa Challengesandunmetneeds-thebreadthofpreclinicalworkongoing(OP1) Geneticoverview/currentRDEBknowledge(OP14) Morphological andmorphometricalanalysisofcutaneoussquamouscellcarcinomainpatientswith Wound healingmechanisms–macrophages(OP6) Skin microbiomecharacteristicsofdystrophicepidermolysisbullosapatient(P25) Read-throughtherapeutics:drugre-purposingforEBpatients(OP18) Efficient genomeeditingforcorrection ofrecessivedystrophicepidermolysisbullosainiPScells using Fromtheorytopractice–translationalmedicineintoclinicaltrials (OP22) PEBLES (OP20) RDEB-SCC protocols(rigosertib,pembrolizumab,cetuximab&nivolumab,SCCcream)(OP16) A caseseriesofsixpaediatriccaseswithlaryngo-onycho-cutaneoussyndrome(LOC) (P10) Immunefunctionandbacterialchallenge(OP7) Fibrosis inEB–mechanismsandanti-fibroticstrategies(OP10) Novel playersintheestablishmentandprogressionoffibrosisrecessivedystrophic Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Tuesday 21 Wednesday 22 5.00–5.45 4.50–5.00 4.40–4.50 2.25–4.10 10.55–1.25 1.25–1.55 9.35–12.25 9.00–9.35 8.50–9.00 8.40–8.50 8.30–8.40 Vicki Chen: carboxymaltose: asingleinstitution,observational,retrospectivestudy(P39) Ashjan Alheggi: Cristina Has:Molecularandmutationalsignaturesofsquamouscellcarcinomasinepidermolysisbullosa(P2) Karen Snelson:GuidelinesforthecareofadultswithEBundergoing clinicalandsurgical procedures(P6) st Anterior segmentspectraldomainopticalcoherencetomographyinepidermolysisbullosa(P120) January 2020–Oralposterstationpresentations Mauro Perretti: Catriona Crombie: Planningforclinicaltranslation(OP46) Brett Kopelan: Elena Pope: Dedee Murrell: EBrelevantendpoints(OP43) Current dilemmas–adebate-Measurement andResearch -Chair:JouniUitto Sharmila Collins:Partnershipapproachtoresearchfunding(OP42) Brett Kopelan: Break bench tobedside(OP40) Kathrin Dieter: Suma Krishnan:B-VECoff theshelftopicalgenetherapyforDEB(OP39) Mary Spellman:A taleoftwotherapeuticapproaches-anupdateonclinicalstudiesindiacereinandFCX-007(OP38) Theresa Podrebarac: Recombinantcollagen7:asystemicapproachtoRDEBtherapy(OP37) Jean Tang: Large wounds:anupdateonnaturalhistorydataandEB101(OP36) Johann Bauer:Introduction–clinicaltrialdesign(OP35) Clinical trials&research programmes: Chair:JohannBauer for autosomaldominantEpidermolysisBullosa(P86) Hiroyuki Morisaka:PossibleapplicationofbroadandunidirectionalgenomeeditingusingthenovelCRISPR-Cas3system Dystrophic EpidermolysisBullosa(P81) Alain Hovnanian: Fernando Larcher: Stateoftheartgeneediting(OP27) Gene manipulationandtherapies:Chair:Jakub Tolar Jose Bonafont Arago: Jose Oral poster presentations Mark Sumeray:Non-viralgenetherapy(OP34) Ulrich Koller: Peter vanden Akker: Peter Marinkovich: Jouni Uitto: Laura deRosa:Hologeneprojects(OP29) Pavel Rotschein: Anna Bruckner:CASEREPORT: SCCmanagementandresponse(OP67) Clinical andmanagementcase histories:Chairs:EliSprecher/Hana Buckova Tariq Khan:Podiatry(OP66) Catina Bernardis: Surgery forSCC(OP65) Gill Smith: (OP63) Irene Lara-Corrales:Anaemia Antonia Reimer: Michael Baertschi: Susanne Kramer:Oralhealth(OP60) David Albert: Joe Curry:Gastrostomy(OP58) Anna Bruckner:Oesophagealmanagement(OP57) Katie Plevey: Eli Sprecher: SuperficialEBS/peelingskinsyndromes(OP55) Update onclinicalmanagementstrategies:Chairs: Anna Martinez&IgnaciaFuentes Peter Marinkovich: Al Lane:FundingforEBresearch(OP53) Johann Bauer:Allocationofresearchfunds(OP52) Leena Bruckner-Tuderman: Individualisedtherapies(OP51) Current dilemmas–adebate-Funding Challenges-Chair: Al Lane Cristina Has:Advancesindiagnostics/phenotyping(CPG)(OP50) Anna Martinez:ClinicalchallengesofEBskin-insideandout(OP49) Sophie Kitzmueller: nd January2020-Plenary Treatment ofmultifactorialanaemiainadults withsevereepidermolysisbullosausingintravenousferric Handsurgery –managementstrategies(OP64) NextgenerationsequencingapplicationsformutationdetectioninEB(OP30) Qualityoflifemeasures(OP44) Wound care(JEB)(OP56) ENT (OP59) COL17A1editingusingCRISPR/Cas9(OP33) Regulatoryperspectivesandchallenges(OP45) Partnerships -charities,regulatorsandindustry(OP41) ABCB5+ mesenchymalstemcellsforthetreatmentofrecessivedystrophicepidermolysisbullosa–from Innovativetherapeuticdevelopment(OP47) Growthpatterns(OP62) CASEREPORT: SCCmanagementandresponse(OP68) EBGRAFT andadvancesinskingraftingusingimprovedvectors(OP28) Eye (OP61) Update-EB-CLINET (OP48) Gene therapyforRDEB(ex-vivovsin-vivo)(OP31) Costs andaccessibility(OP54) ExonskippingforRDEB(OP32) CRISPR/Cas9-based geneeditingstrategiesforclinically-relevant EB2020 1 st WorldCongressonEpidermolysisBullosa ex vivo Acta DermVenereol Suppl220 correctionofRecessive 3 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta 4 Wednesday 22 Thursday 23 Jouni UittoandJemimaMellerio 5.30 CloseoftheCongress 4.45–6.15 3.20–4.45 1.55–2.50 Tobias Zahn:LosartanforEB,or'Ittakesavillagetoraisechild'(P47) Suma Krishnan:ResultsfromaPhaseI/IIstudyoftopicalgenetherapy(bercolagenetelserpavec,B-VEC)inpatientswithrecessive Mark O’Sullivan: The effect ofrockerbottomfootwearonfootbiomechanicsandthedevelopmentplantarblistersinpatientswith Catherine Miller: 4.40–5.25 2.30–3.55 12.15–1.15 11.35–12.15 9.40–10.55 9.05–9.40 dystrophic epidermolysisbullosa(RDEB)(P52) epidermolysis bullosasimplex;apilotstudy(P93) EB2020 1 rd Rachel Torkington-Stokes: Gilles Brackman: The impactofantimicrobialresistanceontopicaltreatmentselection(OP82) and AP 103(OP81) Mark Sumeray:DevelopmentoftwotopicalapproachestowoundhealinginEB. An updateonprogresswithOleogel-S10 Erik Gerner: Strategies for care –statusupdate:Chairs: Anna Martinezand Anja Diem Michael Hund:Innovationinpatientdataplatforms(OP79) Godfrey Fletcher: Christine Bodemer: Bahar Dasgeb:EB-associatedSCC: The Jefferson Adult EBandComplexSkinCancerClinic(OP76) Danielle Greenblatt: Ravi Hiremagalore: ManagingEBinaresourcelimitedsetting(OP74) Jemima Mellerio: Support models:Chairs: Anna Martinezand Anja Diem Hagen Ott:PruritusinEB(OP72) Boris Zernikow:Preventionandtreatmentofpain(OP71) Margarita Calvo: Nic Schrader:Cannabinoids––painanditch(OP69) Quality oflife(pain&itch):Chair:MariekeBolling Rachel Box,JaneClapham,Lynne Hubbard, SusanneKramer, SusanaMorleyMarkPopenhagen EB communityopenforum–askthepanel:Facilitator:Jemima Mellerio Susanne Kramer:Oralhealth(clinicalguidelineinEB)(OP104) Lynne Hubbard: Nutrition(OP103) Danielle Greenblatt: Petra deGraaf:Psychosocialguidelines(OP101) Jennifer Chan: Amy Price: Kattya Mayre-Chilton: Updates inEBclinicalcare: Chairs:JemimaMellerio& Agnes Schwieger-Briel Sam Geuens:Educationandfamilysupport/care&socialservices(OP97) Brett Kopelan&SimoneBunting: Natasha Harper& Assya Shabir:Qualityoflife–clinicianandpatientworkingtogether(OP95) Living withEB:Chairs: Anja Diem& Anna Martinez Godfrey Fletcher: Christine Prodinger: Challengesofclinicaltrialdesign(OP93) Sharmila Collins&LenaRiedl: Gabriela Petrof: Clinicaltrialsexplained(OP91) Current dilemmas–adebate-Patients inclinicaltrials-Chair:JouniUitto Brett Kopelan: Anna Martinez:Advancesinclinicalmanagementstrategies(OP89) Jemima Mellerio: Peter Marinkovich: Su Lwin:Researchupdate(celltherapy)(OP86) Updates inEBresearch: Chair:JouniUitto Brett Kopelan/JimmyFearon: DEBRA International/co-ordinationandcollaboration(OP85) Evanina Morcillo Makow: A globalapproach toEB:Chair:Brett Kopelan January2020–Plenary nd January, 2020–Oralposterstationpresentations st Hand ContractureDevelopmentinChildrenwithRecessiveDystrophicEpidermolysisBullosa(P42) WorldCongressonEpidermolysisBullosa The importanceofexerciseinEB(OP99) A potential new therapeutic approach targeting wound infection – disrupting bacterial communication (OP80) Biotechcommercialdevelopment(OP90) OccupationaltherapyinEB(OP100) Smallfibreneuropathy(OP70) Cancer&cancertherapeutics(OP88) Usingregistriesandbigdata(OP94) Multidisciplinary teambestpractice(GSTT)RareDiseaseCentre(OP73) International EBpatientregistry(OP78) Researchupdate(geneandprotein)(OP87) Educationalprogrammes(OP77) Telemedicine(OP75) EBandpregnancy(OP102) Clinicalpracticeguidelines,patientversionsandEBinfographics updates(OP98) DEBRAsaroundtheworld–a40yearhistory(OP84) The roleofHydrofiberdressingsinEBwoundmanagement(OP83) Patient andparentperspectives(OP92) Familyandcommunity(OP96) Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV applications. novel aspects of pathophysiologyandpossiblenovel therapeutic ture ofEBshouldbeanimportanttarget ofresearchtouncover studied inpatients.Otherapproachestargeting the systemicna this regardcelltherapiesandseveralsmallmoleculeshavebeen or suppressingsecondaryfeaturesofEBhasbeenevaluated.In delivery ofmedicationthatisrecreatinglostgeneexpression body viametabolicandepigeneticconsequences. Thus systemic mation processesleadingtothosesequelaecanaffect thewhole bronchopulmonary and urogenital epithelial systems. The inflam esophageal, the in defect adhesion the of consequence direct as defined be can symptoms Systemic recently. investigated been have epithelium stratified the on therapies local to approaches deficiencies in epithelial structures of the body. Several promising The primary gene defect discovered in variants of EB leads to pital Salzburg Department of Dermatology, EB House Austria, University Hos- Johann Bauer FOR RESEARCH EB AS A SYSTEMICDISEASE –IMPLICATIONS OP3 features of EB. A reliable tool for identification of splicing errors. clinicians and researchers, emphasizing both clinical and genetic to both value of be should scheme classification proposed The provision ofcare. under theEBumbrellaintermsofmedicalandsocioeconomic considered be should disorders “EB-related” these fragility, skin fragility. Because of the common manifestation of skin with disorders tissue connective and disorders, hyperkeratotic disorders,erosive disorders, gories. skin peeling include These skin cleavage is very superficial, are classified as separate cate are aminorpartoftheclinicalpictureornotseenbecause the prototype. Other disorders with skin fragility, where blisters represents EB classical which of fragility, skin with disorders clinical andmoleculardata. We introducetheconceptofgenetic disorders withskinfragility, withafocusonEB,basednew in the most recent consensus expert meeting we re-classified the consensus meeting on epidermolysis bullosa (EB). In April 2019, international last the of report the of 2014 in publication since identified been have subtypes clinical and genes new Several burg, FacultyofMedicine,UniversityFreiburg, Germany Department of Dermatology, Medical Center - University of Frei- Cristina Has OTHER DISORDERS WITH SKINFRAGILITY INHERITED EPIDERMOLYSIS BULLOSA AND CONSENSUS RE-CLASSIFICATION OF OP2 No abstractsupplied cine, ThomasJeffersonUniversity, Philadelphia,PA USA mel Medical College, and Jefferson Institute of Molecular Medi- Department of Dermatology and Cutaneous Biology, Sidney Kim- Jouni Uitto BREADTH OF PRECLINICAL WORK ONGOING CHALLENGES AND UNMET NEEDS- THE OP1 ORALLECTURE ABSTRACTS - - - precisely controlthedynamicsofmacrophagefunctionalplasti important target totreatdisease. The moleculardeterminantsthat an as emerged have macrophages cancer, and diabetes 2 type pathological processes, from chronic inflammatory skin diseases, inappropriate macrophageactivationunderliesabroadrangeof those intoahostprotectivewoundhealingresponse.Giventhat andintegrate ofinjuredtissue sense avarietyofenvironmentalcues Blood monocytesthatarerecruitedtothesideoftissuedamage of thebody’s innateabilitytorestoretissuefunctionafterinjury. of themonocyte/macrophagelineageareanintegralcomponent Cells differentiation. and growth tissue inflammation, of stages sequential in proceeding program cellular dynamic complex, a mechanical injuries. Skin injury extending into the dermis induces the organism from diverse external threats including infections and outer barrierofthebodyandhasintrinsicmechanismsthatprotect The skinprovidesalife-sustainingstructuralandimmunological Germany Department of Dermatology, University of Cologne, Cologne, Sabine Eming OF MACROPHAGES WOUND HEALINGMECHANISMS– THE ROLE OP6 No abstractsupplied St John’s Institute of Dermatology, King’s College London, London John McGrath STRATEGIES CURATIVE VS DISEASEMODIFYING OP5 No abstractsupplied Freiburg, Germany Freiburg Institute for Advanced Studies School of Life Sciences, Leena Bruckner-Tuderman ENVIRONMENT MODELLING EBIN THE RESEARCH OP4 RDEB patients. wound healing conditions, including perturbed wound healing in could offer anewapproachtopharmaceuticallytargetand impaired response healing the of outcome the impacts activation, 2 type- specifically activation, monocyte/macrophage shaping and targeting that RDEB. We indicate with that findings present will fibril crosslinks in excessive scarring and carcinogenesis in patients the interplaybetweentype2-activatedmacrophagesandcollagen a criticalroleincarcinogenesis. We postulatea functional rolefor indicates that these specific type collagen fibril crosslinks play also type collagen fibril crosslinks in skin fibrosis. Emerging evidence wound macrophagesincontrollingthedevelopmentofbone-like We uncoveredafundamentalroleoftype2cytokine-activated healing and epidermal carcinogenesis in patients with RDEB. role of myeloid cell activation at the interface of disturbed wound the Further,understand response. to repair aim physiological we dinate their functional plasticity duringthesequential phases of the pathways andtranscriptionalnetworksinmacrophagesthatcoor beginning to emerge. We are interested to understand signalling city duringhealingprogressionarelargely unknownandarejust Oral lectureabstracts Acta DermVenereol Suppl220 5 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta signs and physical examination, biochemical testing and the use the and testing biochemical examination, physical and signs bility and efficacy were evaluated over a period of 2 years by vital million ADMSC per kilo were administered every 21 days. Tolera Medicines (AEMPS). Three separate intravenous injections of 1 ethical approvalandpermission fromtheSpanish Agency of treatment wasprovidedasacompassionate useexceptionafter to painfulintraorallesionsandconstantitching. The cell-based with ahighdiseaseburdenandpoorqualityoflifemainlydue patient RDEB a to treatment efficient and safe a provide to tive gingival application). ADMSC wereadministeredwiththeobjec intralesional injectionofplatelet-richplasmaandhyaluronicacid lidocaine, anesthetic corticosteroids, (topical treatments local of managing thesymptoms.Oralulcerswererefractorytoavariety barely was antidepressant- and inhibitor pump proton tramadol, analgesics, opioid antagonists, –H2 treatment pharmacologic tissue (ADMSC)aretherapeuticallysuperior. Long-termsystemic processes. Itisnotclearwhethertheonesderivedfromadipose these attenuate to able be to shown have tissues, different from isolated (MSCs), cells stromal Mesenchymal disease. the of den and inflammation play a relevant role in the progression and bur disease with multiorgan involvement in which, fibrosis, infection Recessive DystrophicEpidermolysisBullosa(RDEB)isasystemic (UC3M), Spain Department of Biomedical Engineering-Carlos III University María JoséEscámez CLINICAL RESEARCH OP8 should furtherrefinetheaboveoutcomes. those with dystrophic and junctional EB. Completion of this study in particularly patients, EB in formation scar and healing wound tissues. This collateraltissue damagemaycontributetodelayed ses andhealingcancauseconsiderabledamagetohostcells healthy controls.Neutrophildysfunctionduringimmunerespon spectively, rendering them different from EB simplex patients and with regard to higher ROS release and higher apoptosis rates, re Clustering ofdatawasnotedforjunctionalanddystrophicEB eity of neutrophil responses, ranging from hypo- to hyper-reactive. data analysisrevealedthatEB patients display markedheterogen in response to physiological and experimental stimuli. Preliminary monitor neutrophil antimicrobial mechanisms as well as cell death, and analysed by fluorescence- and luminescence-based assays, to blood neutrophilswereisolatedbydensitygradientcentrifugation matched healthy controls are currently being recruited. Peripheral based uponfrequencyandlocationofblistering. Age- andgender Dystrophic, junctional EB, and EB simplex patients were enrolled time, the immune function of first systemic neutrophils the in for EB patients. characterise, to is study observational ongoing this have abnormal apoptosis rates. Therefore, one of the key aims of excess reactive oxygen species (ROS), cytokines or proteases, or release they when particular in health, tissue on effects mental healing. Itisknownthatdysfunctionalneutrophilshavedetri range ofantimicrobialmechanismscrucialtohostdefenceand during biologicalwounddebridementinhealing. They exhibita and infection of sites at responders first the and cell immune of and/or healingtherapies.Neutrophilsarethemostabundanttype a fundamentalprerequisitefordevelopingnovelantimicrobial is patients these in response inflammatory-immune the standing Under scarring. and healing delayed sequelae, infective to lead disorders characterisedbyrecurrentblisterformation. This may Epidermolysis bullosa(EB)encompassesagroupofraregenetic Birmingham DentalSchool&Hospital,Birmingham,UK Josefine Hirschfeld CHALLENGE IMMUNE FUNCTION AND BACTERIAL OP7 6 EB2020 1 st WorldCongressonEpidermolysisBullosa ------Department of Inflammation, Division of Medicine, University of Medicine, College London Division Inflammation, of Department David Abraham LEARNINGS FROMOTHERDISEASES OP9 their therapeuticrationaluse. MSCs inthemodulationofpatient’s immunecellstoimprove fashion. Resultssuggestthatiscriticaltoexploretheeffect of safe and transiently efficacious treatment of RDEB in a systemic of conceptaboutuseadiposetissueasasourceMSCforthe the health improvement. In conclusion, we provide the first proof killer, non-classical monocytes and granulocytes- correlated with Interestingly, changes in PBLs memory T cells, CD56bright natural cytometry.flow by analyzed were (PBLs) populations leukocyte were moderated/normalizedafterthe ADMSC-treatment. Blood circulating levels of positiveandnegativeacute phase reactants status ofthepatientwassecondaryaimthisstudy. Altered immunologic and inflammatory the in ADMSC of impact sible may underlie the failure to suppress the emergence of B cells that produce IL-10 when stimulated through innate immune pathways, tion of IL-6 and IL-8. This, in concert with their reduced ability to of B cell subsets (transitional B cells), and their increased produc scleroderma. These studieshavealso revealedaltereddistribution in autoantibodies hallmark specific of development the in role highlightedtheir has inimmune-mediated disease subpopulations a target forintervention. The increasingunderstandingofBcell for patient stratification aswell as importance in pathogenesis and nent to T cell function, and in addition proposes the complosome IL-17 and altered IFNg:IL-10 ratios. This data is especially perti Upon activation, these cells exhibited elevated levels of IL-6 and pathological CD4+ T cellcomplosomesignatureinscleroderma. a identified cells T activated and resting by expression cytokine regulating Th1 responses.Deepphenotypingandassessmentof of theroleintracellularcomplementsignaling(complosome) immune-mediated diseases. This research relates to the observation has recentlyemerged thatishighlyrelevantto T cellfunctionin A newandpotentiallyexcitingareaofstudy T cellbiology pathway. response IFNγ of modulation and signaling cell and hypoxia, glycolysis, of upregulation the including pathogenesis disease in implicated genes for enriched significantly signature identified changes in the scleroderma macrophage transcriptome studies exploringisolatedmonocyte-derivedmacrophageshave with susceptibilitytodiseaseorsubphenotypes.Recent and genomesequencinghasbeguntoidentifygenesassociated GWASgene, Candidate pathology. disease perpetuating and observations ontheroleofmonocytes/macrophagesininitiating the autoimmunediseasesclerodermahavebuiltuponprevious of importantpathogenicevents.Innateimmunologicalstudiesin modulators and mediators critical emphasized also have profiles mune cell phenotypes and cytokine, chemokine and growth factor the immune system (innate andadaptive) andallied changesinim autoantibodies andassociatedclinical endotypes. Dysregulationof with links clear the context, disease the in and transcriptomics, overlapping studies including those focusing ongenetics and diseases. The prominent role of inflammation arises from several mation as a key process in the pathogenesis ofautoimmune Evidence from clinical and laboratory studies places cell inflam the drugmedicationdoseswerereduced.Understandpos Simultaneously, pain-VASscores. and LIS BEBSS, EBDASI, the muco-cutaneousconditioncorrelatedwithadecreasein without major adverse reactions. The significant improvement in that improvedheroverallconditionincludingqualityoflife quality of life the (QoL-5D). on The patient impact experienced transient the benefits and (LIS) (VAS),itching pain BEBSS), and (EBDASI pathology cutaneous for scales clinimetric specific of - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV designed, sincethisiscurrently notinthemarket. planned. Forthistrialapediatric formulationforlosartanisbeing trial to assess the efficacy of losartan in RDEB is currently being Based on the promising data of the interim analysis, a phase II/III fibrotic and inflammatory markers in the circulation are presented. RDEB-related clinical manifestations. In addition, initial data on tion and fibrosis, by showing different scoring systems to assess all present first data on the efficacy of losartan in reducing inflamma on safetyandtolerabilityoflosartaninRDEBwerepositive. We in aserioussafetyconcernswereobservedduringthetrial. The data 18 patients completed the trial. No severe complicationsresulting and a delay in theprogress. We performed an interim analysis after for RDEB, we expect an amelioration of the disease manifestations on the efficacy of the drug. Although losartan would not be a cure in children with RDEB aged 3-16 years, but also to gain first data objective of the trialis to evaluatesafety and tolerability of losartan The 2017. June in initiated was RDEB with children in losartan in RDEB. The phase I/II clinical trial REFLECT on the use of progression cancer skin facilitating and phenotype fibrotic the role of TGFβ in mediating injury-driven inflammation, generating This isbasedonourpreclinicalresearchthatuncoveredakey alleviate RDEB symptoms by targeting excessive TGFβ activity. remains veryhigh. We proposeanevidence-basedapproachto disability. No cure exists for RDEB, and the unmet medical need contractures andmittendeformitiesofhandsfeetcausesevere sive squamous cell carcinomas. Among the many symptoms, joint and wound healing, which favours development of highly aggres blistering skin follows fibrosis progressive Severe involvement. RDEB ischaracterizedbylife-longskinfragilityandmulti-organ burg, FacultyofMedicine,Freiburg, Germany Department of Dermatology, Medical Center-University of Frei- Dimitra Kiritsi INTERNATIONAL PERSPECTIVES LOSARTAN FORRDEB TRIAL –RESULTS AND OP11 of dermalfibrosis. progression the during events specific with interfere to designed preclinical evaluationofnovelsymptom-relieftherapiesforRDEB from learned lessons and data present will I addition, In RDEB. in progression disease fibrotic of understanding the in advances mechanisms atplayinRDEBisneeded.Iwilldiscussrecent efficacy ofsymptom-relief therapies detailed knowledge of disease severer form to a milder form of RDEB. However, to improve the mechanisms secondarytolossoftype VII collagencanskewa cell carcinomas.Previousworkhasshownthattargeting disease squamous cutaneous metastasizing early-onset, for propensity DEB (RDEB)–thecombinationoftheseeventsresultsinhigh sue fibrosis. In its most severe form – generalized severe recessive fragility, impaired antibacterial immunity and progressive soft tis bullosa (DEB), a monogenic disease characterized by chronic skin Genetic lossoftype VII collagencausesdystrophicepidermolysis University ofFreiburg, Freiburg, Germany Department ofDermatology, MedicalFaculty, MedicalCenter– Alexander Nyström FIBROTIC STRATEGIES FIBROSIS INEB–MECHANISMS AND ANTI- OP10 and/or tractableforthedevelopmentofeffective therapeutics. or selective for certain autoimmune diseases, useful as biomarkers across diseases and to define aspects that are likely to be specific and assesscommonorsharedfeaturesunderlyingautoimmunity mechanism(s) driving cell inflammation are paramount to delineate produce scleroderma specific autoantibodies. Studies on biological - - - neoadjuvant, concomitant and adjuvant strategies (and combi (and strategies adjuvant and concomitant neoadjuvant, the contextofregimensdeliveredwithcurativeintent.Induction/ either anti-EGFR/anti-HER orimmunotherapies have been used in underpinned thedevelopmentoftreatmentapproachesinwhich recent advancesinpatientswithrelapsed/metastaticdiseasehave of these novel therapy opportunities in HNCwill be discussed. Our (anti-CD137, anti-GITR, anti-CD40, anti-OX40) signals. A range agonistic or anti-NKG2A) anti-TIM3, (anti-LAG3, antagonistic disease virus, vaccinia virus); and novel antibodies which provide agonists); oncolytic virotherapies (herpes simplex virus, Newcastle (toll-like receptor agonists, stimulator of interferon activators gene (STING) immune innate antigens); viral or mutations specific tumour- private (against vaccination cancer including: agents, combination novel adding by therapies, platform these on build metastatic HNC within the last 5 years. Ongoing research seeks to received FDA and EMA approvals for use in patients with relapsed/ and first-line settings5. Both nivolumab and pembrolizumab have outcomes in R/M HNC in both second-line (platin-refractory)3,4 toimprove ligandhavebeenshown death-1 receptorandits antibodies thatblockinteractionsbetweentheanti-programmed checkpoint-inhibitory immune recently, More chemotherapy2. of relapsed/metastatic(R/M)diseaseincombinationwithcytotoxic locally-advanced diseaseincombinationwithradiotherapy1and of treatment standard-of-care of part is cetuximab, antibody, neck cancer(HNC)inthe15years. The anti-EGFRmonoclonal mentation ofnoveltargeted andimmunotherapiesforhead There hasbeenhugeprogresswiththedevelopmentandimple Targeted Therapy Team, TheInstitute ofCancerResearch, London Kevin J.Harrington CANCER OF THE HEAD AND NECK PRECISION MEDICINEFORSQUAMOUSCELL OP13 No abstractsupplied Italy Laboratory ofMolecular and Cell Biology, IDI-IRCCS,Rome, Giovanna Zambruno MIRNA INDEB OP12 to the toxicities of novel therapies, especially as they relate to cutaneous effects, willbeconsidered. relate they as especially therapies, novel of toxicities the to the setting of curative treatment regimens.Finally, issues relating fluence practice in both HPV-positive and HPV-negative HNC in from patients with R/M HNC and considering how this might in anti-cancer vaccineswillbediscussed byreviewingavailabledata to improving disease control in this context. The role of adjuvant surface ofcancercellscanalsobeviewedasapowerfulapproach regimens. Specific immunization against antigens expressed on the future useofanti-PD1/anti-PD-L1drugsinconcomitant/adjuvant reference totheirdifferences andthepossibleimplicationsfor and ImVoke-10 [NCT03452137]) will be presented with specific [NCT03040999] KEYNOTE-412 [NCT02952586]8, neck and designs of key registrational trials in this area (JAVELIN-100 head lance atatimewhenonlyminimalresidualdiseaseispresent. The is basedonthenotionofenhancedanti-cancerimmunosurveil patients with HNC. In contrast, the use of adjuvant immunotherapy appear to have the potential significantly to improve outcomes for afatinib7, have been largely negative and these approaches do not inhibitor, pan-HER the and lapatinib6, agent, EGFR/anti-HER2 anti-HER-targeted therapies, data from studies involving the anti- to permanent growth arrest or cancer cell death. For anti-EGFR/ that is needed for cancer survival and growth will, ultimately, lead addiction and the premise that prolonged blockade of a pathway oncogene of concept the on rests efficacy potential of basis the theoretical bases of efficacy. For anti-EGFR/anti-HER therapies, nations ofsuchapproaches)areallpotentiallyfeasibleandhave Oral lectureabstracts Acta DermVenereol Suppl220 7 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta 8. Yu Y,and avelumab of NY.trial Lee III Phase a JAVELIN100: Neck and Head 7. Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, Romanov I, 6. Harrington K, Temam S, Mehanna H, D’Cruz A, Jain M, D’Onofrio I, Manikhas Psyrri G, TaharaD, Castro Soulieres de R, M, Greil KJ, Harrington B, Burtness 5. Soria A, MJ, L, Ahn Licitra J, Dinis TourneauC, Le D, EEW,Soulières Cohen 4. Har Colevas L, J, Licitra Guigay AD, Jr,J, G Fayette Blumenschein RL, Ferris 3. J, Erfan S, Rottey A, Kawecki E, F,Remenar Rivera R, Mesia VermorkenJB, 2. these enzymes, collectively called “APOBEC” enzymes, are sub mutations thatleadtocancer. Work is ongoingtounderstandhow role intheimmunesystemtoattack skincells’ DNA andcause mes thathavebeensubvertedin RDEBawayfromtheirnormal Genetic analysis has also identified a group of endogenous enzy cancer, should be made available for trials in patients with RDEB. of patients with SCC in the oral mucosa, so-called head and neck in RDEB. In particular, therapies that are approved for treatment promise in treatment of other types of SCC, may also have benefit emerging therapies, such as immune based approaches that show which leadtocancerarenotuniqueRDEBandthatnew mucosa. These observations suggest that many ofthe mechanisms other squamouscellcarcinoma(SCC)foundinskinandtheoral play a role in cancer development, are similar when compared with frequently detectedinmanyseparatecancersandarethoughtto shown that mutations in “driver-genes”, so-called because they are risk. RecentworkcharacterizingthegeneticsofRDEBcancershas areatincreased who ofEB (RDEB) sub-type dystrophic recessive complication. Cancerisespeciallyimportantinpatientswiththe threatening, life major, a is (EB) bullosa epidermolysis with Squamous cell carcinoma (cancer) arising in the skin of patients Thomas JeffersonUniversity, Philadelphia,USA Andrew South KNOWLEDGE GENETIC OVERVIEW/CURRENT RDEB OP14 1. References 8 Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur 15: 687-694. chemoradiation forlocallyadvancedheadandneckcancer. FutureOncol.2019; the Head and Neck: A Randomized Clinical Trial. JAMA Oncol. 2019 (in press). as Adjuvant Therapy After ChemoradiotherapyinSquamousCellCarcinomaof rington K, Cohen EEW; LUX-Head & Neck 2 investigators. Afatinib vs Placebo Asarawala N, Nicolau UR, Rauch D, Even C, Wang B, Gibson N, Ehrnrooth E, Har Nangia CS, Chaves-Conde M, Kiyota N, Homma A, Holeckova P, Del Campo JM, Vermorken J, Bourhis J, Tahara M, Martins Segalla JG, Psyrri A, Vasilevskaya I, Study. JClinOncol.2015;33:4202-9. the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of Lapatinib andConcurrentChemoradiotherapyFollowedbyMaintenance Silvanto J, Amonkar M, Ahmed N, Santillana S, Bourhis J. Postoperative Adjuvant N, Biswas-Baldwin N, Legenne P, Wissel P, Netherway T, Farrell J, Ellis C, G, Wang-Horvath Z, Sun Y, Dietzsch S, Dubinsky P, Holeckova P, El-Hariry I, Franklin 2019 (inpress). Lancet study. 3 phase open-label, randomised, a (KEYNOTE-048): neck and chemotherapy forrecurrentormetastaticsquamous-cellcarcinomaofthehead investigators. Pembrolizumabaloneorwithchemotherapyversuscetuximab KEYNOTE-048 the of behalf on D, Rischin F, Jin JD, Cheng B, Zhang Y,Gumuscu A, Roy RG, Mendoza R-L, Hong WZW, Ishak T, Rordorf N, haiboon A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamp 2019; 393:156-167. study.Lancet. 3 phase open-label, randomised, a (KEYNOTE-040): carcinoma docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell rington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, JP,Machiels P,Zhang B, Burtness R, Mehra N, Mach RF,Swaby J, Cheng Har of theHeadandNeck.NEnglJMed.2016;375:1856-1867 Carcinoma Squamous-Cell Recurrent for JW,Nivolumab Shaw ML. J, Gillison Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit rington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, 2008; 359: 1116-27.Med. J Engl N cancer. neck and head in cetuximab plus chemotherapy Platinum-based R. Hitt N, Amellal A, Schueler C, Bokemeyer D, Raucourt De Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, noma oftheheadandneck.NEnglJMed.2006;354:567-78. Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carci squamous-cell for cetuximab plus Radiotherapy KK. EK, Ang Rowinsky Youssoufian N, J, H, Amellal Baselga MS, Kies R, Ove J, Jassem D, Raben R, EB2020 1 st WorldCongressonEpidermolysisBullosa ------The developmentofaggressivecutaneoussquamouscellcarci Foundation Trust, London St John’s Institute ofDermatology, Guy’s andSt.Thomas’ NHS Jemima Mellerio & NIVOLUMAB)PEMBROLIZUMAB, CETUXIMAB RDEB-SCC PROTOCOLS (RIGOSERTIB, OP16 No abstractsupplied Freiburg, Germany Freiburg Institute for Advanced Studies School of Life Sciences, Leena Bruckner-Tuderman THERAPIES FOREB ASSOCIATED CANCERS INTERDISCIPLINARYMANAGEMENT AND OP15 preventing cancer. symptoms may also show benefit to patients by delaying or even and burden disease reducing of goal the with fibrosis prevent to and cancer development. In this context therapies being developed ongoing to identify therapeutic targets which may is reduce fibrosis work and patients, RDEB in progression cancer of a major mediator as fibrosis identified has research cancers, SCC other Finally, in addition to identifying similarities between RDEB and with drugssuchthatcancercanbedelayedorevenprevented. verted to cause cancer and whether their activity can be inhibited repurposing ofagentsapproved foranumberofothercancerty in access to new and expensive immunotherapy drugs. However, variability geographical significant with therapy, of mencement sentation andadvancecancompromise rapidapprovalandcom of thesetumoursandthepotential shorttimespanbetweenpre with smallanddisparatepatient cohorts. The aggressivenature difficulties with fraught be can trials clinical formal that means targets forEBSCCs;beingararecomplicationofdisease therapeutic new identifying to challenges significant are There SCCs whichshouldbe starting recruitment in comingmonths. the way foraclinical trial of oral or IV use in advanced RDEB cells SCC EB for toxicity preferential has which (PLK-1) inhibitor,rigosertib, kinase-1 polo-like the of Identification weeks. 3 or 2 seem tobegenerallywell-toleratedbutrequireIV infusionevery although profiles effect side variable have drugs These lacking. regression inadvancedEBSCCsbutformalclinicaltrialdata is stabilisationorpartial lumab andcemiplimabmayresultindisease reports is, at present, limited. Anecdotally, pembrolizumab, nivo recent considerationinEBSCCsalthoughthenumberofpublished many different cancers. They have also becomean area formore antibodies have been a major development in the armoury against may beimpairedduringtreatment.Programmeddeath-1(PD-1) access maybeanissueinEBandwoundhealingatothersites cycles, (IV) intravenous weekly in Given treatment. of initiation be atendencyforgreaterimpactontumourgrowthwithearlier may there although disappointing, generally and mixed been EB-related SCCs to the EGFR inhibitor, cetuximab: results have for furtherstudy. A handfulofpublicationsdetailtheresponse making newertargeted therapies attractive andanimperative area responsive to conventional chemotherapy agents and radiotherapy, this form with of EB. adults In addition, for RDEB SCCs death are usually of very poorly cause leading the this making readily, metastasize and aggressively behave SCCs clearance, surgical Despite primaries. multiple developing most with and removal, arise atsiteswhichmaybechallenginganatomicallyforsurgical age, with frequency increasing with onwards adolescence from particularly theseveregeneralisedform. Tumours tendtoarise (RDEB), bullosa epidermolysis dystrophic recessive with duals nomas (SCCs)remainsoneofthebiggestchallengesforindivi in vitro andinanvitro mousechimeramodelhaspaved ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV ointment orvehiclewasapplied toerosivewounds3timesaday mutations who had little or no C7 in their skin. Gentamicin 0.1% led, clinical study on five RDEB patients with COL7A1 nonsense vitro data in hand, we then performed a blinded, vehicle control cultures readily generated full-length, functional C7. With this doses ofgentamicinandtwo other aminoglycosidestothese increasing of addition the However, C7. full-length synthesize not did cells these that showed and culture into fibroblasts and length C7 leading to new AFs. We placedRDEB keratinocytes mutations inthe COL7A1 gene and safely produce newfull- aminoglycosides such as gentamicin could read-through nonsense and Duchenne’s’ MuscularDystrophy. We soughttodetermineif mutations in patients with Hailey-Hailey Disease, Cystic Fibrosis antibiotics havebeenshowntobeableread-throughnonsense 30% of these mutations are nonsense mutations. Aminoglycoside – 25 about but described, been have gene) COL7A1 (the C7 for with exuberant scarring. Over 300 mutations in the gene encoding fragility,skin marked heal that wounds erosive and blisters, skin main two layers of skin, the epidermis and dermis, which causes and anchoring fibril structures (AFs) at the interface between the treatment. RDEB patients lack functional type VII collagen (C7) threatening, blistering disease for which there is no current curative Recessive dystrophicepidermolysisbullosa(RDEB)isalife- California Los Angeles, The KeckSchoolofMedicine, University of SouthernCalifornia, David T. Woodley PURPOSING FORRDEB READ-THROUGH THERAPEUTICS: DRUGRE- OP18 in youngpatients. particular in EBS, of treatment systemic or local the for suitable be inreach. We expectthatcompoundC1orrelativesmightbe clinical use for treatment of other diseases, clinical studies should intercellular adhesioninESA assays.GiventhatC1isalreadyin strengthens and aggregation keratin reduces significantly which C1 compound present I chaperoning. and inflammation rylation, have identified several compounds which target protein phospho We(ESA). assays sheet epidermal performed we adhesion, cell candidate compoundsnotonlyreducedaggregationbutimproved ber and sizeof aggregates were reduced. To examine whether and used artificial intelligence to identify cells in which the num compounds chemical ~5.500 of screen content high a performed we K14R125C, expressing keratinocytes EBS Using skin. EBS that canbeappliedasacreamororallytoimprovethequalityof ming to prevent or revert aggregation, using chemical compounds aggregation mechanisms, we are developing a therapy approach ai tion andcontributetoitch.Basedonourunderstandingofkeratin keratin mutations compromise cell adhesion, increase inflamma susceptible and result in extensive cell/tissue fragility. Moreover, into cytoplasmicaggregates. These renderkeratinocyteshighly and KRT whichcausethecollapseofkeratincytoskeleton Most EBSformsarecausedbymissensemutationsinKRT5 Leipzig University, Germany Institute ofBiology, DivisionofCell&Developmental Biology, Thomas M.Magin DISEASE INFLAMMATORYTARGETINGEB ASAN EBS TARGET AND TREATMENTOPTIONS/ OP17 blish formalclinicaltrials. their experiences and strive, where possible and feasible, to esta treatments. ItisimperativethattheEBmedicalcommunityshare anti-cancer new potential finding to ever than closer us brings pes, and preclinical research identifying EB SCC-specific agents in ------cin, buthavenotyetbeentestedinaclinicaltrial. such as amlexanox, may also have a similar potential to gentami AFs in their skin. Other non-aminoglycoside, read-through drugs topically, intradermally or intravenously and generate new C7 and gest that gentamicin may be safely administered to RDEB patients In addition to gathering baseline data, the study involves data cap children with different forms ofrecessive dystrophic EB (RDEB). and adults from data economic health and laboratory subjective, lecting a broad and comprehensive set of data col covering objective, 2014, November since running been has (PEBLES) Study The ProspectiveEpidermolysis Bullosa LongitudinalEvaluation Foundation Trust, London,UK St John’s Institute of Dermatology, Guy’s andSt Thomas’ NHS Jemima E.Mellerio PEBLES OP20 time willnotallowdiscussionofallthese. stages ofrecruitment. There areothertopicaltherapiesintrialbut final the in is which DEB and JEB for RCT III phase vehicle vs were issueswiththeplaceboeffect inthistrial;topicaloleogel there why and EB, of forms all for vehicle vs RCT 6% lantoin Topical sirolimusforEBsimplex–themethodology; topicalal vs intralesional gentamicin for RDEB, which has been published. damage/scarring. The studies that will be reviewed include topical blisters, erosions) whilst longer term studies may show (erythema,changes in activity/inflammation disease in changes measure tion separatelyfromlongertermdamage;shortstudiescan inflamma scoring including measures, outcome subjective and objective validated using same, the dressings keeping by effect pemphigoid. In such studies, it is important to reduce the placebo profound impacts in other rare blistering diseases, such as bullous randomized controlledtrials(RCTs). Topical therapieshavehad types of evidence include case reports, independent and sponsored misreading prematureterminationcodon(PTC)mutations. The targeting ofEBgenesandtargeting recessiveformsofEBby specific inflammation, downstream targeting including nisms, Topically applied therapies for EB can work by several mecha Australia Dept Derm, St George Hospital, UNSW andUniversity of Sydney, Dedee F. Murrell BULLOSA TOPICAL THERAPIES FOREPIDERMOLYSIS OP19 laboratory tests after treatment. Taken together, or these function studies renal sug audiograms, their in alterations no were there daily for 2 weeks or twice weekly for 3 months. In these 7 patients, intravenous gentamicin (7.5 – 10 mgs/kg) to similar RDEB patients clinical trial in which the results are still pending, we administered Inanotheron-going observed. orrenalfunctionwere values blood or skin. No alterations in hearing (audiograms), laboratory skin, the patients did not generate anti-C7 auto-antibodies in their blister formation.DespitetheformationofnewC7inpatients’ new decreased and closure wound improved exhibited wounds, placebo-treated not but wounds, Gentamicin-treated injections. observed at sites treated bygentamicin topically orbyintradermal placebo-treated test sites had few or no AFs, while new AFs were new C7wasobservedinplacebo-treatedsites.Pre-treatmentand No skin. normal in observed that of 165% and 20% between C7 new generated gentamicin patients, 5 all respectively.In (IEM), staining with anti-C7 antibodies and immuno-electron microscopy expression of C7 and AFs evaluated by immunofluorescence (IF) months after treatment, the treatment sites were biopsied and the were injectedintointactskinsitesfor2days. At 1monthand3 vehicle saline a or gentamicin patients, same the In weeks. 2 for Oral lectureabstracts Acta DermVenereol Suppl220 9 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta lection includes clinical features and management, laboratory test rica. JAMA Dermatol. 2019;155(2):196-203). Ongoing data col Events inPatients With Epidermolysis BullosaFromNorth Ame (Feinstein Jetal. Assessment ofthe Timing of MilestoneClinical of patients enrolled through June 30, 2017 was recently published esophageal dilation, first squamous cell carcinoma, etc. A summary first placement, tube gastrostomy as such events), Milestone led diagnostic information, and objective, initial clinical events (cal demographics, includes data Baseline care. routine scheduled, center. Patientsareenrolledandreviewedwhentheypresentfor coordinating data current the Colorado, of University to moved the database was based at Stanford University. In 2015, the CCOD 2011when in started CCOD the in Enrollment practice. clinical best for guidelines refine and develop to order in EB of ventions longitudinal data on the course, complications, and clinical inter participate infuturestudiesandtherapeutictrials;2)togather CCOD are: 1) to identify well-described patient cohorts that may the primaryresearchprojectofEBCRC. The overallgoalsofthe EB Clinical Characterization and Outcomes Database (CCOD) is 2010, it now includes 20 sites in the US, Canada, and Mexico. The CRC) is aNorth American multisite research network. Formed in The EpidermolysisBullosaClinicalResearchConsortium(EB Colorado School ofMedicine,Children’sUniversity ofColorado Hospital Anna Bruckner DATABASE CHARACTERIZATIONOUTCOMES AND EPIDERMOLYSIS BULLOSA CLINICAL OP21 the studytootherEBsubtypes. expand to term, longer and possible, as RDEB with individuals expand tointernationalEBcentresgatherdatafromasmany to recruitment, UK continue to is aim Our complications. and the PEBLES data include bone health and gastrointestinal disease of analysis for areas Future £97,943. was total annual mean the were alsogreatestinRDEB-GS;combinedwithdressingscosts and £1,699 pa (SD £2,800) in RDEB inversa. Costs for paid care intermediate, generalised RDEB in £19,414) (SD pa RDEB-GS, £10,112 in £68,875) (SD pa £85,156 of median a revealed of dressingsandretentiongarmentsin different formsofRDEB gical adjustmentofindividualstotheirRDEB. Analysis ofcosts with smaller numbers of participants. This may reflect psycholo was reportedfromparentsandchildrenusingthePedsQL toolbut from physicalratherthanemotionalfunctioning. A similartrend duals with RDEB-GS had greatest impact on QOL, predominantly Adult qualityoflifewasassessedwiththeQOLEBtool;indivi GS) whoalsoexperiencedgreatestsleepdisturbancefrompain. and procedural, particularly in generalised severe RDEB (RDEB- background both common, very also was Pain therapies. current medication for itch, probably highlighting the lack of efficacy of any taking not are individuals of majority the this, Despite tion. on different aspects of life including sleep, mood and concentra common symptominallRDEBsubtypeswithanegativeimpact extremely an is Itch care. of costs and life of quality pain, and and adultswithRDEB.Initialdataanalysishasfocussedonitch children 60 recruited has PEBLES date, To EB. for treatments costly potentially new, of development the justify to indicator burden ofcaringforEBandserveasahighlyrelevantuseful Granular analysisofthecostscarecanhighlighteconomic or prognostic indicators that are relevant for clinical management. markers surrogate reveal may laboratory, or subjective clinical, variables, different of comparison addition, In EB. in studies the aimtoidentifypotentialclinicalendpointsforfuture with life, throughout data intra-individual establishing annually) ture at regular intervals (6-monthly in under 10 year olds, thereafter 10 EB2020 1 st WorldCongressonEpidermolysisBullosa ------developed to address pain, itch, wound care and fibrosis. Para fibrosis. and care wound itch, pain, address to developed being are trials treatments, symptomatic better for need pressing early phase clinical trial stage. In parallel, and acknowledging the editing, protein replacement and drug treatments are reaching the EB. Specifically, efforts in the areas of cell and gene therapy, gene for muchmoreeffective treatments andthepotentialforacure new translational therapies offering for the first time opportunities to this apply to drives fresh witnessed has years 10 to 5 last the amount has been learnt and applied in clinical practice. However, genetic diagnosis, counselling and prognostication, a preimplantation tremendous and prenatal diagnostics, to knowledge this of 20 genes implicated in different subtypes of EB with application the 1990s through to the current state of understanding with over of start the from discovery gene EB, of diagnosis the in antigens BMZ against antibodies monoclonal of introduction the (BMZ), on based EB the planeofblisterformationatbasementmembranezone of types main the delineating 1960s the in work momentum overrecentdecades.FromPearson’s ultrastructural ing different formsofepidermolysisbullosa(EB)havegathered Advances inourunderstandingofthepatho-mechanismsunderly Foundation Trust, London St John’s Institute ofDermatology, Guy’s andSt.Thomas’ NHS Jemima Mellerio TRIALS TRANSLATIONAL THERAPY INTO CLINICAL FROM THEORY– TOPRACTICE OP22 microbes, diagnostictesting,andpatientreportedoutcomes. ced by recent collaborative studies on skin care practices, wound stage andtreatmentgoals. combining therapeuticapproaches tailoredtotheiruniquedisease patients improved pain relief and slower progression ofdisease by coding, nutritional support, and protective bandaging. We can offer ditional therapies include local topical treatments, ABCB5 protein grafts ortoinjectintochronicwound sitesisanotheroption. Ad genome-edited ornaturallyrevertantcellstocreatebio-engineered grafts ormesenchymalstem/stromalcells.Usingthepatient’s own epidermal like products, cellular additional provide to donor the donors. The acquiredimmunetoleranceofthepatientallows to usehaplotype-matcheddonorsincreasesthe pool of available transplant conditioning regimens make BMT safer, and the ability the onlycurrenttherapythatcanimpactinternaltissues.Milder is that BMT benefits. significant offers approaches several therapy combines personalized cure, a of absence the In time. over cumulative are scarring and inflammation, infection, of impact the as evolving, and unique is presentation patient’sdisease EB the potentialtoimprovequalityoflifeforthesepatients.Each to thediscoveryanddevelopmentofsystemictherapiesthathave led has it but curative, been not has (EB) bullosa epidermolysis Using bonemarrowtransplant(BMT)totreatseverevariantsof University ofMinnesota,USA Blood and Marrow Transplantation, Department of Pediatrics, Jakub Tolar TREATMENT FOREB SYSTEMIC BMT AND COMBINING APPROACHES: OP23 of approachescurrentlybeingexplored. charities is key to reaching potential benefits across the spectrum ans, researchers, patients, industry and support organisations and clinically meaningfulendpoints.Collaborationbetweenclinici of afullerunderstandingthenaturalhistorydiseaseand mount tothesuccessofclinicaltrialsinEBisdevelopment enable EBCRC investigators to better understand EB, as eviden results, and patient reported symptoms and outcomes. These data - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV months (7 evaluation points). Currently, we are evaluating efficacy from the baseline once a monthafter the drug administration for 6 primary endpoint, we evaluated change rate of the total lesion area a day, 4 days in the first week, followed by 2 days in the 2 the in days 2 by followed week, first day,the a in days 4 once infusion minutes’drip 30 by mg/kg 1 of dose a at patients systemically administered the HMGB1 peptide drug to the RDEB (three times)todeterminethebaselineoflesionarea. We then and ulcers)ineachRDEBpatientsonceamonthfortwomonths erosions (blisters, lesions skin RDEB the of area total evaluated HMGB1 peptide. Prior to administering the HMGB1 peptide, we Nine RDEB patients are involved in the phase IIclinical trial ofthe peptide drugforpromoting regeneration ofthe RDEB skinlesions. started investigator-initiated phaseIIclinicaltrialoftheHMGB1 and epidermal components. With these scientific backgrounds, we as RDEBskinandpromotesregenerationofbothmesenchymal circulating mesenchymal stem cells in the necrotic injuries such marrow-derived bone of accumulation induces which medicine, have developedHMGB1peptidedrugasaregeneration-inducing nents oftheepidermalstemcellnichesmustberegenerated. We To recover functional skin, both the epidermal and dermal compo destroy thedermalmicroenvironmentsbyseverescarformation. repetitive blistering all over the skin. RDEB patients eventually continuously deplete epidermal stem cell populations due to (RDEB)patients bullosa epidermolysis Recessive dystrophic Medicine, OsakaUniversity, Japan Department of Stem Cell Therapy Science, Graduate School of Katsuto Tamai NIEHCES INRDEBSKIN FOR REGENERATING EPIDERMAL STEMCELL DEVELOPMENT OF HMGB1PEPTIDEDRUG OP25 II studiesforfurtherclinicalevaluation. 1 yearaftergenetherapy. These dataprovidearationaleforphase transgene andsubsequentC7restorationinvivotreatedskinat COL7A1 of presence the with therapy gene fibroblast lentiviral of efficacy potential and safety demonstrating study human first mature new no detected. were ToAFs the is this knowledge, our but subject, 1 in 12 month at skin injected the in demonstrated was cDNA) oftransgene(codon-optimizedCOL7A1 The presence jects, with a sustained increase up to 12 months in 2 of 4 subjects. in the injected skin compared with noninjected skin in 3 of 4 sub 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity (P significant a was efficacy, there Regarding C7. binant serious adversereactionsorautoimmuneagainstrecom without tolerated, well were fibroblasts Gene-modified skin. injected the in transgene of presence morphology,and AF sion, against recombinant C7. Secondary outcomes included C7 expres reactions autoimmune including safety, was outcome primary months. The 12 for up followed were and fibroblasts autologous injections (~1 × 106 cells/cm2 of intact skin) of COL7A1-modified label phase I trial, 4 adults with RDEB each received 3 intradermal kinase promoter for phase I evaluation. In this single-center, open- COL7A1 cDNA underthecontrolofahumanphosphoglycerate self-inactivating lentiviralplatformencodingacodon-optimized a developed We skin. in (AFs) fibrils anchoring of constituent main the (C7), collagen VII type membrane basement coding form ofskinfragilitydisorderduetomutationsinCOL7A1en Recessive dystrophic epidermolysis bullosa (RDEB) is a severe don, UK St John’s Institute ofDermatology, King’s College London, Lon- Su Lwin DYSTROPHIC EPIDERMOLYSIS BULLOSA FIBROBLAST GENE THERAPY FORRECESSIVE OP24 and 4 th weeks, totally 10 times administration in a month. As a As month. a in administration times 10 totally weeks,

< nd 0.05) , 3 , rd - - - - - , internal epithelia. mesenchymal stem cells (MSCs) can facilitate wound healing in assessing ifthesystemicdeliveryofgene-corrected-iPSC-derived often require the use of feeding tubes. Therefore, we which are currently RDEB, with associated manifestations gastrointestinalsevere the treating in effective be not will cells these patients, keratinocytes maycorrectthecutaneousphenotypeinRDEB iPSC-derived gene-corrected While scarring. and inflammation superior outcomesforRDEBpatientsduetothelowerriskof potentially produce togrowepidermalgraftsandwould takes decrease thetimetopatientapplicationvs.andcostit would system delivery “spray-on-skin” the successful, If grafts. RDEB iPSCsasamorestraightforwardalternativetoepidermal Medical, for delivering skin cells differentiated from gene-edited evaluating a “spray-on-skin” delivery system developed by Avita is lengthy and consequently expensive. Therefore, we are currently required togeneratethesegraftsfromgeneticallycorrectediPSCs time the patients, RDEB for therapy iPSC-based an of efficacy grafts maybethefastestpathforwardtodemonstratesafetyand Col7 protein, as detected by immuno-staining. Although epidermal lines successfullydifferentiated intokeratinocytesandexpressed iPSC corrected All modifications. genetic off-target observable characterized iPSClineswerekaryotypicallynormalandhadno all and 5% as high as efficiencies Wecorrection gene. observed founder c.7485+5G>A (IVS98+5G>A)mutationintheCOL7A1 netically correctediPSCsfromthreeRDEBpatientssharingthe ge produced we protocol, this of robustness the Totest weeks. into a one-step procedure which can be performed within 5-6 together withRNA-basedCRISPR/Cas9-mediatedcorrection protocol reprogramming RNA-based high-efficiency reported previously our combined have we iPSCs, corrected genetically To reducethenumberofstepsassociatedwithgeneration tive Medicine,UniversityofColorado Department ofDermatology, Director, GatesCenterforRegenera Dennis Roop FROM GENE-EDITEDIPSCS METHODS FORDELIVERINGCELLSDERIVED STATEIPSCS ANDALTERNATIVEOFTHE ART OP26 comparable to those detected in normal carrier keratinocytes, sho over 40% in primary keratinocytes, producing C7 protein levels, efficiencies showed strategy correction gene HDR-based the every cell in the bulk population expressing functional C7 while, val close to 90% in primary RDEB keratinocytes, with practically With the NHEJ approach, we achieved efficiencies of exon remo donor template-carrying AAV, aiming to precisely correct the gene. using Cas9 asRNP to create double stand breaks in the DNA anda designed a marker free HDR-based strategy for RDEB correction, Spain an other Latin American countries. More recently, we have because aframe-shiftmutationinthisexonishighlyprevalent target a as chosen was 80 Exon COL7A1 keratinocytes. patient efficient mutation-containing COL7A1 exon removal in primary highly achieving electroporation, by delivered complexes Cas9 step NHEJ-basedcorrectionprotocolconsistingofdualgRNA/ one- a shown have Recently,we tools. editing genome different rection ofpathogenicmutationsinCOL7A1genebymeans of ourresearch is to achieve highly effective and precise cor Mutations inCOL7A1arethecauseofRDEB. The maingoal of Bioengineering,UC Epithelial Biomedicine Division,CIEMAT-CIBERER, Department Fernando Larcher STATE OF THE ART GENEEDITING OP27 and safetyoftheHMGB1peptidedruginRDEBpatients. 3 M, Madrid,Spain Oral lectureabstracts Acta DermVenereol Suppl220 11 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta profile. Secondary outcomes include efficacy (clinical assess (clinical efficacy include outcomes Secondary profile. safety, knowing that pre-clinical studies showed a safe integration hospital forsick children inParis. The primary endpoints are the UKandgraftedindepartmentofHematologyatNecker Hospital inMadrid.SubjectswillbereferredfromFranceand Jesus will begeneratedinthedepartmentofGenetherapyatNiño and demand. The GMP geneticallycorrectedskinequivalents chronic orrecurrentwoundsaccordingtosubject’s preference keratinocytes and genetically fibroblasts into a fibrin gel to treat autologous skinequivalentgraftsmadeofgeneticallycorrected such asthermalorchemicalburns oftheocularandskinsurface keratinocytes arecurrentlyused to restoresevereepithelialdefects efficacy. Cultured clinical long-lasting ensuring transplantation cells canbecultivatedandgenerate autologoussheetssuitablefor stem epithelial conditions, culture appropriate the Under cells. requires thecultivationandtransplantation ofepithelialstem therapy cell keratinocyte-mediated of success the life, during surface epitheliaexperienceacontinuousself-renewalprocess or repairingseverelydamagedtissuewithculturedcells.Since Cell therapyisanemerging therapeuticstrategyaimedatreplacing cine “StefanoFerrari”,Modena,Italy Holostem Terapie Avanzate S.r.l., CenterforRegenerative Medi- Laura DeRosa HOLOGENE PROJECTS OP29 of lifeandpreventionskincancer. quality improved allowing RDEB, of treatment permanent for the promise of a safe and efficient 4-year additionallongtermfollow-upperiod. This studyholds a with M12) and M6 M3, M2, M1, (at months 12 for followed of C7antibodiesand T-cell responsetoC7. The subjectswillbe andimmunetolerance bydetection inthegraftedskin) transgene morphology,fibril anchoring of expression, presence C7 ment, cm 300 to up receive will subject Each tially grafted. The two first subjects have already been enrolled. grafting and nohistory ofskin cancer. Three subjects will be ini for suitable sites multiple C7, against antibodies neutralizing circulating of absence (C7), collagen VII type detectable of levels low RDEB, severe to moderate have Subjects features. from FranceandtheUKwithoptimalclinicalbiological and efficacy of this treatment. We have identified eight subjects open-label proof-of-conceptstudyaimingatevaluatingsafety activating) retroviralvector(Orphandrug).Itisa single-center genetically correctedwithaCOL7A1-encodingSIN(SelfIN epidermolysis bullosa(RDEB)usingautologousskinequivalents trial aimingatgraftingadultsubjectswithrecessivedystrophic EBGRAFT isaninternationalexvivogenetherapyphaseI/II hospital forsickchildren, Paris,France SERM UMR1163 ImagineInstitute, University ofParis,Necker Department ofGenetics, Laboratory ofgenetic skin diseases,IN- Alain HovnanianandEBGRAFT partners IMPROVED VECTORS USING EBGRAFT AND ADVANCES INSKINGRAFTING OP28 approaches totheclinic. corrected bulk keratinocytes, enables the easy translation of both correction coveringawidernumberofmutations. The useofgene gene precise a offers strategy HDR-based Otherwise, removal. applied to other mutation-containing exons suitable for exon NHEJ-based approach offers a therapeutic option that could be regenerationwhentransplantedontonudemice.healthy skin normal a support to able efficiency correction gene remarkable adhesion inregeneratedskin.Bothgenomeeditingtoolsoffer a wing that these are feasible strategies to restore dermal-epidermal 12 EB2020 1 st WorldCongressonEpidermolysisBullosa ex vivogenetherapyapproach 2 of COL7A1-modified of - - - cine, ThomasJeffersonUniversity, Philadelphia,PA USA mel Medical College, and Jefferson Institute of Molecular Medi- Department of Dermatology and Cutaneous Biology, Sidney Kim- Jouni Uitto FOR MUTATION DETECTION IN EB NEXT GENERATION SEQUENCING APPLICATIONS OP30 platform forthetreatmentofEpidermolysisBullosa. arises the HOLOGENE projects aimed at cell and gene therapy features oftheindividualandgeneticmutation.Inthiscontext specific the strategy,on patient-oriented built a is future the for LAMB3 patients. Based on these studies, what can be envisioned clinical trialaimedatex-vivogenetherapyofselectedJEB- evidences promptustoproposetheimplementationofapivotal gene correctioninepidermalstemcellsfromJEB-patients. These the demonstrationofsustainedtransgeneexpressionandstable availability ofsurgical protocolsforgraftinglarge areas;(iii) skin cultivating and transplanting large areas of the epidermis, (ii) the patient treated demonstrated: (i) the feasibility and possibility of retroviral vectorexpressingtheß3chainoflaminin-5. The last transduced and JEB laminin-5-deficient epidermal stemcellsisolatedfromthreepatientssuffering from of the adhesion properties of stratified epithelium obtained from ponent laminin-332. We show here full phenotypic correction databases inheritableskindiseases, suchasEB. provide a reliable first-tier diagnostic approach to extend mutation extends molecular diagnostics of rare genodermatoses, and it can RNA-Seq” “clinical Thus, approaches. sequencing DNA-based ting inaberrantsplicing;these mutations wereundetectableby synonymous-exonic anddeep-intronic sequencevariantsresul identified RNA-Seq example, an plots. As Sashimi by sualized vi as RNA of patterns splicing altered and analysis, heatmap consequences on transcriptome expression as quantitated by their and mutations of identification for used be also could but approaches, DNA-based to similar mapping homozygosity and informatics analytical steps. bio RNA-Seq allowed variant calling appropriate with EB, of forms different with families on recently appliedwhole-transcriptomesequencingbyRNA-Seq technologies improves the diagnostic yield significantly. We have transcriptome sequencingbyRNA-SeqwithotherNGS-based and gene expression at RNA levels. Thus, combination of whole- splicing on impacting those particularly mutations, the of many consanguinity. However, with DNA-based analyses failed to identify families in genes candidate of identification in assisted homozygosity mapping, based on DNA polymorphism, has also as whole-exomeandwhole-genomesequencing.Genome-wide (NGS), including use of gene-targeted sequencing panels as well on DNA analysisbynext-generationsequencingtechniques ders. MutationdetectionstrategiesinEBhavelargely focused currently underdevelopmentforthisgroupofintractabledisor specific mutations is a prerequisite for allele-specific treatments and genes mutant the of information the Moreover, diagnosis. forms thebasisforprenataltestingandpreimplantationgenetic and the overall outcome. Knowledge of the genetic defects also severity disease the of prognostication allowing and sification, subclas with diagnosis the of confirmation for important is Identification of mutant genes and pathogenic sequence variants the cutaneousbasementmembranezoneandinepidermis. in expressed genes 21distinct manyas inas mutations with Epidermolysis bullosa(EB)iscurrentlyknowntobeassociated by mutationsingenesencodingthebasementmembranecom bullosa (JEB)isasevereandoftenlethalgeneticdiseasecaused and DystrophicEpidermolysisBullosa.Junctionalepidermolysis Junctional of case the is this deal, be can disease genetic skin a damage irreversibly. When the cell therapy meets the gene therapy ex-vivo with a gamma ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV is to ameliorate the most severe RDEB phenotypes due to biallelic is toamelioratethemostsevereRDEB phenotypesduetobiallelic protein production reinitiated. The ultimate aim of exon skipping and bypassed are way,mutations That mRNA. mature the from signals in order to exclude in-frame exons harboring null mutations splice- exonic block to RNA-molecules) modified chemically Exon skipping uses antisense oligonucleotides (ASOs; synthetic, and Dermatology, Groningen, theNetherlands University Medical Center Groningen, DepartmentsofGenetics Peter C.vanden Akker EXON SKIPPINGFORRDEB OP32 or synergistic, howeverthisremainstobetested. that theseexvivoandingenetherapiesmaybecomplementary epidermal autograftsachievedinrecentyears.Itisquitepossible a groupinItaly/AustriawhoarebuildingonprogressfromJEB and equivalents, skin autologous fibroblast and epidermal rected cor gene employed be will who France in one including trials, up speedinthenearfuturewithgroupseuropeenteringnew RDEB has been fast paced and exciting, and will continue to pick of therapy gene with progress the total, In stage. trials clinical 3 settings. The B-VEC therapy is also approaching the pivotal phase RDEB patientsworldwidewhodonothaveaccesstospecialized many reach to potential the with biopsies, for need the without in a home setting, as well as off the shelf shipping of the products would be ease of application as a wound dressing gel, ultimately be as durable as the not present, these therapies would theoretically not be expected to approach would be that while the risk ofinsertional oncogenesis is even uponrepeatedreapplication.Disadvantagesoftheinvivo positive effects ondurable wound healingwithoutsafetyissues ports of the B-VEC therapy indicates robust molecular correction, re interim unavailable, and blinded still are data skipping exon the pediatric. While are which of 4 patients, 10 in used been has replication incompetent HSV-1 -COL7A1 vector (B-VEC)which patients. The other approach involves a topical gel containing a adult two and pediatric 2 including Stanford, at 3 treated, been functional collagen VII protein. In this approach, 4 patients have still by truncated slightly a of production and skipping, 73 exon containing oligonucleotideswhichactattheRNA leveltoinduce participated in two such approaches. The first involves a topical gel approach is in vivo COL7A1 gene therapy forRDEB. Stanford has and cell production needs to be tightly coordinated. An alternative operating room or day procedure unit, and the timing of shipping to patientsrequireshospitalizationincludingplacementeitherin proach requires a manufacturing run on each patient, applications ap each addition, In detected. been yet have cancers no and this having thegenetransferoccurexvivolimitssystemicriskof tional oncogenesis due to the vectors that are employed, however pivotal phase3trials.Drawbacksincludeatheoreticalriskofinser entering now are studies and safety and efficacy of record track ex vivogenetherapiesarethattheyhavedemonstratedthelongest jected into both intact skin and chronic wounds. The advantages of with grafts total). 5 adults and one pediatric patient have been treated autologous epidermalmonolayergrafts(6perpatient patients. 7 adults have been treated with treated with gene therapy at Stanford so far, including 7 pediatric lecular correctionofRDEB.Intotal26RDEBpatientshavebeen cal trialsemployingseveralpromisingnewtechniquesinthemo Our grouphas been active in studying a groupofearly phase clini Stanford UniversitySchoolofMedicine,Stanford CA,USA Department ofDermatologyandProgram inEpithelial Biology, M. PeterMarinkovich (EX VIVOGENE THERAPYRDEB VS FOR OP31 ex vivo COL7A1 treated autologous fibroblasts which are in ex vivo therapies described above. Advantages ex vivo COL7A1 treated IN VIVO) = 42 ------which isaprerequisiteforfurthersystemic ASO-development. skin, RDEB non-blistered in work also may skipping exon that human skinafterintradermalinjection. These datademonstrate specific of skipping induce indeed can novel and efficacy of exon skipping ASOs in intact human skin using a protein canbereached. We arecurrently studyingthedelivery skipped the of levels expression considerable provided tations, the mostsevereRDEBphenotypescausedbybiallelicnullmu ameliorate to potential the has skipping exon Hence, phenotype. the severe less the protein, skipped the of expression the higher type wildtype for RDEB on study previous our the collagen, VII from generalizedseveretolocalizedacralphenotypes. As seenin patients carrying recessive natural exon skipping variants ranged ping hasafutureassystemictherapyforDDEB.Phenotypesin We thereforeconcludedthatitisquestionablewhetherexonskip within thespectrumofDDEBcausedbyglycinesubstitutions. associated withthedominantnaturalexonskippingvariantswere required asecondvariantintranstocauseRDEB. The phenotypes duced natural exon skipping, of which 15 acted dominantly and 12 applications. All butone(atopical RNA therapy)useaviral vector trials, both as cell-based therapeutics and direct to patient topical Gene therapiestotreatEBarebeing testedinpreliminaryclinical Amryt PharmaceuticalsDAC,Dublin, Ireland Mark Sumeray LYSIS BULLOSA NON-VIRAL GENE THERAPY FOREPIDERMO­ OP34 tic basisofthediseasewithoutneedforsinglecellexpansion. using CRISPR/Cas9paired nicking topermanently treat the gene strate thedevelopmentofanexvivo gene editing therapy for JEB, revealed a C17 restoration efficiency samples of of analysis FACS samples. treated bulk in efficiency) 49% (> level protein and efficiency) 38% RNA(> the at shown efficiency of tes, we maintained a highly efficient allele-specific gene disruption Upon nucleofection-mediatedRNP deliveryintoJEBkeratinocy off-target activityandnoimpairmentofon-target geneediting. (RNPs). PairingofCas9nickasesisassociatedwithareduced JEB patientkeratinocyteswithpairednickingribonucleoproteins of a frameshift mutation responsible for JEB, we treated primary (JEB) patients. Aiming attheCRISPR/Cas9-mediatedcorrection or absentexpressionofC17injunctionalepidermolysisbullosa membrane zone.COL17A1mutationstypicallyleadtoareduced of basalkeratinocytesandthelaminalucidabasement for maintainingtheconnectionbetweenplasmamembrane Type XVIIcollagen(C17)isatransmembraneproteinessential tal oftheParacelsusMedicalUniversitySalzburg, Genodermatoses, DepartmentofDermatology, University Hospi- EB House Austria, Research Program forMolecular Therapy of Ulrich Koller COL17A1 EDITINGUSINGCRISPR/CAS9 OP33 Registry and literature. We identified 27 mutations thatleadtonaturalexonskippingfromtheDutchEB carrying patients DEB of phenotypes the studied we skipping, mouse model. To determine the potential therapeutic effect of exon concept forCOL7A1 exon 105 skipping null mutations. Previously, we demonstrated successful proof-of- RNP-treated primaryJEBkeratinocytes. These studiesdemon western blot and flow cytometric analysis of unsorted and sorted population. Restored C17 was detectable cell via positive immunofluorescence, C17 the accumulating thereby keratinocytes, JEB However, using FACS we were able to isolate ex vivoskinmodel.Preliminarydatasuggestthatour ASOs > 80%. Further, an efficient Oral lectureabstracts Acta DermVenereol Suppl220 restoration was COL17A1 restoration was > in vitro andinaxenograft COL7A1 COL7A1 exons in intact 50%, without selection. reframed COL17A1 reframed variants thatin variants 13 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta and multiple treatment arms; incorporation of interim data review; and multipletreatmentarms;incorporation ofinterimdatareview; possible. This includes e.g. usage ofmultiple/composite endpoints RD trials is to use the limited available information as efficiently as agenda viaresearchnetworks/consortia. Another keystrategy in institutional policiesaremajor issues tofostertheRDresearch harmonization ofregulatoryand funderrequirementsaswell Likewise, global regulatory strategies and operational execution, needs accurateresourcestoensurequalityandprofessionalism. patibility withoccupationalobligations). Administrative support investigations, literacy, personal financial expenditures and com invasive and visits scheduled of extent travel, time, of terms in policy, which also aims at reducing the patients‘ trial burden (e.g. outcomes andmeasurements procedures as well as information decision on study length, target population, in-/exclusion criteria, design. This involvesaffected individualsandtheircaregiversin agencies andpatientgroupstoencourageapatient-centrictrial e.g. a close collaboration between sponsor, academia, regulatory trial feasibility. Approaches toovercomethesehurdlescomprise impairs critically that challenges regulatory and logistical gical, in children;or(5)increasingtrialcomplexityduetomethodolo concerns touseplacebocontrolsaswellconductresearch riates further limiting data validity andgeneralizability; (4)ethical diseased studycohortwithincreasedrandomimbalanceincova while increasingtrialdurationandcosts;(3)heterogeneityofthe trictions andrecruitmentfailurescompromisingstatisticalpower endpoints, effect size and outcome measures; (2) sample size res mechanisms of intervention, with targets/ subsequent difficultiespotential to define and course natural traits, disease pathogenic into insights limited (1) include to challenges, many faces (EB) Clinical research inrarediseases (RD)like Epidermolysis bullosa University Salzburg Department ofDermatologyand Allergology, ParacelsusMedical Johann Bauer TOCLINICALINTRODUCTION TRIALDESIGN OP35 topical therapyforRDEB. As a non-viral gene vector HPAE shows significant promise as a basement membranezoneofRDEBskinaftertopicalapplications. also shownitcansuccessfullyreturntype VII collagenalongthe toxicity whenappliedtoRDEBcellsinvitro orinvivo.Ithas EB control and pre-transfected group. AP103 has not shown any between detected was difference significant a removed outliers 18 treated animals, 10 were positive for type VII collagen. When grafted RDEBskincultures2weeksaftertreatment.Ofatotalof Topical AP103 application leads to type VII collagen detection in levels. fibroblast normal with compared collagen VII type more 3.5-fold approximately express fibroblasts RDEB collagen. VII compared withnormalkeratinocyteendogenouslevelsoftype is expressed in RDEB keratinocytes after a single AP103 delivery topical applications. Approximately 5-fold more type VII collagen pre-treated with the AP103 polyplexes and then also received three were grafts the or grafts, RDEB the to applied were applications in amurinemodelgraftedwithhumanRDEBskin. Three topical the testing in-vitro lowing tested were polyplexes AP103 to RDEBpatientcellsinvitro to test efficacy and tolerability. Fol maceuticals DAC as AP103. The AP103 polyplexes were applied gene therapyforRDEBcurrentlyindevelopmentby Amryt Phar Dystrophic EB, COL7A1. This complexation forms the non-viral polymer complexedwiththetherapeuticgeneneededtotreat synthetic a (HPAEs)are esters) poly(β-amino branched Highly most promisefor delivery of DNA to the skin of patients with EB. the show molecules synthetic types, three these Of molecules. terms, physical force, inorganic particles and synthetic engineered differentbroad of in methods. range include, a These by mically DNA bynon-viralmethodsis currently beingresearchedacade to deliverthetherapeuticgene. The challengetodelivertherapeutic 14 EB2020 1 st WorldCongressonEpidermolysisBullosa in vivo ------larger, phase3studyisforthcoming. and no serious adverse eventsor systemic retrovirus detection. A form of C7 and anchoring fibrils, woundthe healingin foryears up2 toto 6 years, up for seen correction molecular with subject, to treatthesewounds.Sixchronicwoundsweretreatedineach keratinocyte-based autologousgenetherapyin7adultsubjects pruritic. In 2013, our group initiated a Phase 1/2a clinical trial of within weeks). Chronic wounds are larger, more painful and more and recurrentwounds(whicharedynamic–healingre-opening of RDEB wounds exist: chronic open wounds (which never heal), functional type VII collagen(C7). We haveshownthattwotypes RDEB patients have mutations in the COL7A1 gene, thus lacking Department ofDermatology, Stanford University Jean Tang NATURAL HISTORY DATA AND EB101 LARGE RDEB WOUNDS: AN UPDATE ON 0P36 methods toadaptthesignificancelevelinsmallpopulations. well as to decrease sample size requirements by applying statistical heterogeneity,clinical as of effects mitigate and procedures tion human dermal fibroblasts (FCX-007) at targeted chronic wounds autologous genetically-corrected,COL7-expressing of injections child; ages9to 38 years)withsevere generalized RDEB received 1 adults, (5 patients 6 study, Phase1/2 ongoing an (RDEB).In separation inpatientswithdystrophic epidermolysisbullosa gene encodingtype VII collagen(COL7)causedermal-epidermal was generallysafeandwelltolerated.MutationsintheCOL7A1 1% group and 23.1% of the control group. Diacerein 1% ointment score of clear/almost clear was reported for 39.3% of the diacerein control group (26.9%), but not significantly (p was higher in the diacerein 1% group (42.9%) compared with the proportion ofpatientswhoachievedsuccessontheIGA endpoint in the control group (53.8%), but not significantly (p was numerically greater in the diacerein 1% group (57.12%) than who achieved ≥ score fortheassessedareaat Week 8. The proportionofpatients 2-point reductionintheInvestigator’s Global Assessment (IGA) a least at endpoint, secondary key the and lesions, EBS of area surface the in reduction ≥60% a weeks. endpoint, 8 primary The (n 1% diacerein randomized 54patientswithmoderatetosevereEBSapply study 2 Phase vehicle-controlled, double-blind, randomized, A IL-1β, has been shown to reduce blistering in patients with EBS. of inhibitor an ointment, 1% Diacerein (EBS). simplex bullosa epidermolysis of pathogenesis the in implicated is cytokine, pro-inflammatory a (IL-1β), interleukin-1β of expression The Castle Creek Biosciences Mary Spellman,MD FCX-007 AND DIACEREIN – AN UPDATE ONCLINICAL STUDIESIN A TALEOF TWOTHERAPEUTIC APPROACHES OP38 No abstractsupplied Phoenix Tissue Repair, Boston,USA Theresa Podrebarac APPROACH TORDEB THERAPY RECOMBINANT COLLAGEN 7: A SYSTEMIC OP37 some promise to increase trial acceptability, optimize randomiza design; randomizedwithdrawalfactorialdesigns)hold (such asseries of n-of-1trialsdesign;response-adaptivestudy designs trial clinical alternative Likewise, methods). statistical or formalsynthesisofpreviouslycollecteddata(e.g.Bayesian 60% reduction in the surface area of EBS lesions = 28) orvehicleointment(n = = 26) oncedailyfor 0.2861). An IGA

= 0.9666). The - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV No abstractsupplied Debra of America, NewYork, USA Brett Kopelan INDUSTRY PARTNERSHIPS REGULATORS –CHARITIES, AND OP41 potential candidateforsymptom-alleviatingtreatmentofRDEB. any safetyconcerns. resultssupportour These ATMP aspromising raised not has committee monitoring data the by evaluation far, So baseline. vs. respectively) years, 12-18 and (adults 8.7% and and 23%, iscorEB clinician by 28.2% and 17.7%, and itch 14.6% by by 25% activity EBDASI in reductions with follow-up ficacy 3 5-12years)havebeentreated. Ten ofthemhavecompletedef years; 12-18 4 adults; (7 patients now,13 of As months. 24 for (overall symptom improvement) is monitored for 12 weeks, safety years) to receive 2×106 cells/kg i.v. on days 0, 17 and 35. Efficacy successively enrolled into 5 age cohorts (adult/12-18/5-12/1-5/0-1 international phase I/IIa clinical trial (NCT03529877). Patients are safety and tolerability profile, this ATMP is currently tested in an aconvincingpreclinical shown therapy medicinalproduct.Having anadvanced- cellpopulationformulatedas functional homogenous the MSCsfromdonorskintissueandprocessthemtoahighly have established aGMP-conform manufacturing processtoisolate we RDEB, of treatment cell-based for MSCs develop ABCB5+ tion of inflammatory myeloid derivatives (Webber et al., 2017). To markedly extended the animals’ lifespans via reduced skin infiltra pathways. In a Col7a1−/− mouse model of RDEB, ABCB5+ MSCs mation-dampening andtissue-healingeffects involvingseveral inflam marked showing skin, human in population (MSC) cell found toidentifyanovelimmunomodulatorymesenchymalstem Recently,the ATP-bindingtransporter cassette been has ABCB5 significantly contribute to RDEB disease phenotype and severity. pathomechanisms inflammatory that evidence accumulating the addressing pathways, symptom-relieving disease-modifying, on will notbecomeavailableuntilinyears.Otherapproachesfocus treatments curative challenges, complex to due However, level. protein mRNAor DNA, the at defect genetic the correct to gies developed. Currentlymuchresearchfocusesoncurativestrate be to remain therapies effective trials, clinical and preclinical in While severaltreatmentstrategiesforRDEBhavebeentested RHEACELL GmbH&Co.KG Kathrin Dieter BEDSIDE THE TREATMENT OF RDEB–FROMBENCH TO ABCB5+ MESENCHYMAL STEMCELLSFOR OP40 No abstractsupplied Krystal Biotech,Pittsburgh, USA Suma Krishnan FOR DEB OFFB-VEC SHELF THE TOPICALGENE THERAPY OP39 following theinjectionofFCX-007. weeks 52 to up observed been have tissues, local in expression COL7 with associated trends, healing wound Positive healed. completely was completely healed;nopairedanduntreatedwound tion of FCX-007, 8 of 10 (80%) treated wounds were evaluated as lentivirus (RCL)detected. At 12weeksfollowingtheinitialinjec with no antibody response to COL7 and no replication-competent post-administration weeks 52 to up tolerated well was FCX-007 post-baseline). weeks 4 and 12, 25, (52, injection second a ved All 6 patients received FCX-007 at baseline, and 4 patients recei (confirmed present for 12 weeks or longer in a monitored period). ------one focuson….. of alleffective partnerships. Sowhatresearchprioritiesshould picking thebestresearchprioritiesisfundamentallyatcore therefore and promising, most looks research translational of bit really determinedbywhat’s hotintheresearcharenaandwhat treatments intoclinicbuttheverynatureofthosepartnershipsis in EBresearchisanessentialobjectiveifwe’regoingtogetbetter of researcharecoveredadequately?Formingeffective partnerships need and maximise the impact of funding and make sure that areas a testament tothe desperation felt.Buthowcanweaddresstheir is change lasting cause to unlikely however trials, in participate munity whowaitpatientlyfortreatments. Their willingnessto ethics committeesandindustryallhoveringaroundtheEBcom brand new ones but also have the international regulatory bodies, with before, as funders and researchers same Wenow? the have of coursemalignantskincancer. Sowheredothepartnershipslie the most severe consequences of EB, chronic wounds, fibrosis and of therapies but also attempts to ameliorate symptoms and tackle research intothegeneticsandbiologyofEBtodevelopment diverse. The areas ofEB research have expanded from fundamental midst oftreatmenttrialstherelationshipsaremorecomplexand the in research, fabulous of decades after but source funding a and researcher simpler.dedicated were You a it needed conduct cures. IntheearlydaysofEBresearchpartnershipsneededto the battle lines would be drawn in the fight towards treatments and EB geneswerediscoveredandwiththemanindicationofwhere nose and differentiate EB subtypes but it was in 1991 that the first tegories. Antigen mapping in the 80’s brought us the ability to diag electron microscopy allowed differentiation ofEB into 3main ca 1960’sthe 70’sin and transmission only that was it but 1870, in in Hebra von Ritter Ferdinand by Austria described first was EB Cure EB,London Sharmila Collins FUNDING PARTNERSHIPRESEARCH TO APPROACH OP42 significant advantages for EBDASI over iSCOREB. Outcome iSCOREB. over EBDASI for advantages significant ting byhonoursstudentClare Rogers asaposter. This found in Australia by 6 assessors and is being presented at this mee beenconducted has andiSCOREB ofEBDASI study comparison briefly.reviewed be will A scores these of Each scores. mixed composite/ be not should studies in Ideally,measures outcome together). lab and objective function), and (QOL (subjective iSCOREB the score, mixed one is there finally EB; to specific in damage/scarring. There aresomelabparametersbutnone blisters, erosions) whilst longer term studies may show changes (erythema, activity/inflammation disease in changes measure separately fromlongertermdamage;shortstudiescan inflammation scoring including measures, outcome subjective and objective validated using same, the dressings effectkeeping placebo by the reduce to important is it studies, such In and an oral score; blister counts and an IGA score forEB simplex. score) EB (Birmingham BEBS the index), scarring and activity For objectiveclinicalscoreswehavetheEBDASI(EBdisease QOL andthefunctionalfoothealthstatusquestionnaire(FHSQ). family for score EB-BOD the QOLEB, or EB in life of quality the validated: been have that measures subjective have we box, tool EB the of terms In feasible. and responsive reliable, valid, The idealclinicalendpointscoreforanyskindiseaseshouldbe Australia Dept Derm, St George Hospital, UNSW andUniversity of Sydney, Dedee F. Murrell ENDPOINTS – A DEBATE EPIDERMOLYSIS BULLOSA RELEVANT OP43 Oral lectureabstracts Acta DermVenereol Suppl220 15 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta more partners and include more countries into our network, as network, our into countries more include and partners more trials, or calls for the recruitment of collaborators. We want to find lopments regardingtreatmentsandresearchupdatesonclinical training options, meetings and EB-related events, on recent deve national centers. Ourmembers get informed about worldwide medical specialistssothattheycanactasEBintheir between professionalsandinstitutions. We alsotrainandinstruct We aim to facilitate connection, collaboration and communication EB. of field the in working professionals care health of network therefore importanttoshareknowledge.EB-CLINET builtupa pertise aboutdiseasemechanismsandbesttreatmentoptionsit is have tobeaddressedbymultidisciplinarycare. To buildupex needs Patient’s attention. medical specialized requires disease, Epidermolysis bullosa (EB), as a rare and phenotypically diverse burg,Salzburg, Austria University HospitaloftheParacelsusMedicalSalz- EB House Austria, Department of Dermatology and Allergology, Sophie Kitzmüller IMPROVE CAREFOREBPATIENTS EB-CLINET - A CLINICAL NETWORK TO HELP OP48 No abstractsupplied Mary UniversityofLondon,UK Barts and The London School of Medicine and Dentistry, Queen Mauro Perretti INNOVATIVEDEVELOPMENT THERAPEUTIC OP47 No abstractsupplied LifeArc, UK Catriona Crombie PLANNING FORCLINICAL TRANSLATION OP46 No abstractsupplied Debra of America, NewYork, USA Brett Kopelan REGULATORY PERSPECTIVES AND CHALLENGES OP45 No abstractsupplied Canada Paediatric Dermatology, TheHospitalforSickChildren, Toronto, Elena Pope QUALITY OF LIFEMEASURES OP44 ferent outcomemeasuresaboveinanunbiasedmanner. or VictoriaWilliams,Langan Sinead Werth,dif the address to Hywel as such measures, outcome on experts independent by it wouldbeidealifDebRA sponsoredaconsensusmeetingled separately.field damage Tothis and progress activity compare ters but dose not assess damage and BEBS has5butis unable criteria. In comparison, the iSCOREB has 4 of these 8 parame these of all fulfills EBDASI the way,only standardized this in severity cutoffs. When theEBoutcome measures areassessed validity,andconstruct feasibility and content (MCID), ference dif important clinically minimum change, to responsiveness each instrument should have good inter and intra-rater reliability, measures shouldbesubjectedtoCOSMINanalysissuchthat 16 EB2020 1 st WorldCongressonEpidermolysisBullosa - - - - -

importance ofknowingEBskininsideandoutwillbediscussed. of both the skin, and internal complications are exacerbated. The the onset ofsquamous cell carcinomaorprogressivedeterioration the age of 20 years, often results in a rapid decline of the skin with from 4, Phase onwards. phase this from affective less be to pear ap therapies anti-inflammatory Systemic inflammation. chronic in theskinandinternallywithcontinuedmassivehighlevelsof both severity in progression faster a shows years, 10-20 from 3, Phase beneficial. be to appear also therapy cell stem intravenous as such therapies anti-inflammation and beneficial, highly be Interventions atthisstagesuchasgastrostomyplacementcan puberty. and metabolism iron health, bone growth, pathways: internal main four affect to begins inflammation, chronic to due increase in severity with more extensive skin involvement which, and anaemia. Phase 2, from 18 months to 10 years, sees a steady gain weight reduced with manifest, disease internal of signs first the months, 18 Around involvement. internal any if little very be mirrored by normal systemic inflammatory markers reflecting moon periodwheretherecanbeminimalskinsigns. This iscan honey a as described often is months, 18 to birth from 1, Phase RDEB progressthough4distinctphases. The clinicalchallengesofEBskinchangeovertime.Patientswith Great OrmondStreet NHSFoundationTrust Anna E.Martinez AND OUT CLINICAL CHALLENGESOF EBSKIN-INSIDE OP49 No abstractsupplied Freiburg, Germany Freiburg Institute for Advanced Studies School of Life Sciences, Leena Bruckner-Tuderman THERAPIES INDIVIDUALISED OP51 proved tobeareliabletoolforidentificationofsplicingerrors. been has RNA-Seq particular, In exploited. be should blotting) Western or arrays SNP RNA-Seq, PCR, real-time quantitative ligation-dependent probe amplification, reverse-transcriptase PCR, pathogenic variant is found, additional techniques (e.g.multiplex is therefore recommended to save time and resources. When no filtering for EB genes is able to solve the vast majority of cases and either astargeted EBgenepanelsoraswholeexomewithtargeted NGS, by testing Genetic correlations. genotype–phenotype and enables predictionoftheconsequencesnovelsequencevariants levels. These methodsprovidecomplementary informationthat protein and DNA the both at EB, of characterization molecular genetic testingandIFMshouldbeperformedtoallowcomplete both literature, the on Based rating. quality Network Guidelines Critical Appraisal SkillsProgrammeandScottishIntercollegiate literature. Sixty-four papers were appraised according to the EB Laboratory diagnosis based ona systematic review ofthe We havedeveloped aclinicalpracticeguideline(CPG)for burg, FacultyofMedicine,UniversityFreiburg, German Department of Dermatology, Medical Center - University of Frei- Cristina Has (CPG) ADVANCES INDIAGNOSTICS/PHENOTYPING OP50 difference andincreasethequalityoflifeforEBpatients. EB affects patientsallaroundtheworld. Together wecanmakea - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV of potentialcurativeordisease modifying therapies.Labelingis easily accomodate the potential outstanding value and risk profile isting reimbursement practices within healthcare systems many not general all of these therapies are expected to be expensive, and ex Reimbursement is another potential hurdle to patient access. In cations andappliedundermorebasiclessspecializedconditions. and insteadcanbeshippedoff theshelfasneededtovariouslo general donotrequireautologouscellmanufacturingorbiopsies in therapies vivo In care. clinical and shipping, manufacturing, in the OR or day hospital unit. This requires tight coordination of ted tospecializedmedicalcentersforplacementEBpatients patient biopsies, performed at specialized facilities then transpor therapies requiremanufacturingrunsderivedfromautologous and clinicalsupplyissuesvaryfromtherapytotherapy. Exvivo impact patient access to these emerging therapies. Manufacturing treatments arenowarising. This talkaddressesthehurdleswhich trials, issues of commercialization, costs and accessibility of these As several gene therapies are now moving into pivotal phase 3 Stanford University SchoolofMedicine,Stanford CA USA Department ofDermatologyandProgram inEpithelial Biology, M. PeterMarinkovich COSTS ANDACCESSIBILITY OP54 than youthink.GoodLuck. expensive more always is research budget, your in flexibility Includeare formulatingaplanandcompletingyourapplications. research support.Continuetoobtainpreliminarydatawhileyou in yourcommunityaswellthroughmanyoutsidesourcesof or 3timeslongerthanwhatyouplan.Lookforfundingsources can accomplishaswellrealizingthatyouwillusuallytake2 the funder’s applicationdirections. Neverplanmorethanyou withdraw ormodifyothersubmittedrequests.Preciselyfollow canyou obtain, is funding Once funding. obtain to order in ces funding request often are submitted to multiple funding sour of previousefforts greatly supports futurerequests.Research goals andtherequestingindividual.Successfulcompletion support isapprovedbecauseofboththerequestingresearch want todoandwhatyouarecapableofaccomplishing.Funding Before requestingresearchfundingyoumustknowwhat versity SchoolofMedicine Professor ofDermatologyandPediatrics, Emeritus,Stanford Uni- Alfred Lane FUNDING FOREBRESEARCH OP53 research andcompany-drivenlatestageapproval–directedwork. butions ofapplicantsmightbeablebridgethisgapbetweenbasic within-kindandcashcontri unrestrictedfundingcomes in which loose control over the progress of these ventures. Mixed models, Inevitably academicinstitutionsandpatientorganisations tendto is toout-licenseacademicresearchbiotechnologycompanies. shown that these studies are rather expensive. Thus the usual model cell-based therapiesandotherlate-stageclinicalstudieshave party retainscontroloverthefurtherprogress.Earlystudieson successful modeloffunding.Inthiscasetheinvolvedresearch Basic researchthathascontributedinthisareaistheclassicaland leads todiseaseandhowwecancombatthislossofadhesion. EB have advanced our understanding of how adhesion deficiency The lasttenyearsofresearchintopathophysiologyandtherapy pital Salzburg Department ofDermatology/EBHouse Austria, UniversityHos- Johann Bauer ALLOCATION OF RESEARCHFUNDS OP52 - - - - - Trust, London,UK Great Ormond Street Hospital forChildren NHSFoundation Katie Plevey WOUND CARE(JEB) OP56 molecule may benefit most patients affected with theseadhesion conditions. this targeting interventions that suggesting desmosin, directly orindirectlyresultfromabnormalexpressionofcorneo Peeling skinsyndromesareofparticularinterestastheyoften isolated cutaneousdisorderstolife-threateningcomplexdiseases. extensive genetic heterogeneity andrange in severityfrom mild sub-basal blisterformation). These raregenodermatosesfeature of epidermolysisbullosa(whichareassociatedwithintrabasalor must be considered in the differential diagnosis of classical forms Inherited disordersfeaturingsupra-basalintraepidermalseparation Division ofDermatology, Tel Aviv MedicalCenter, Tel Aviv, Israel Eli Sprecher SUPERFICIAL EBS/PEELINGSKINSYNDROMES OP55 cess ofthesetherapiestopatients. No abstractsupplied Great Ormond Street Hospital NHS Foundation Trust, London,UK David Albert ENT OP59 No abstractsupplied Great Ormond Street Hospital NHS Foundation Trust, London, UK Joe Curry GASTROSTOMY OP58 delay re-strictureafteradilationprocedure. or delaytheonsetofesophagealstricturesandhowtoprevent is littleevidencetoguidecurrentmanagementonhowprevent experienced operators. Recurrence after dilation is common. There of hands the in events adverse of risk low a has which dilation, These strictures are best treated with fluoroscopy-guided balloon A single, proximal esophageal stricture is characteristic in RDEB. patient’s first esophageal dilation procedure is 3 to 4 years of age. Clinical ResearchConsortiumshowthemostcommonagefora will develop a stricture by age 5, and more recent data from the EB National EB Registry show that 50% of patients with severe RDEB associated withrecessivedystrophicEB(RDEB).Datafromthe perforation orruptureoftheesophagus.Stricturesareprimarily cases, rare in and webs, strictures, erosions, and blisters include The esophageal manifestations ofepidermolysis bullosa (EB) Colorado, USA School ofMedicine,Children’sUniversity ofColorado Hospital Anna Bruckner UPDATE ESOPHAGEAL MANAGEMENT: CLINICAL OP57 No abstractsupplied to payersandinsurancecompanies. This alsocanimpacttheac treatments, the greater an argument and justification can be made currently availablenon-genetictherapiessuchasallogeniccell of benefits the beyond extend therapies molecular new these of pivotal trials. The fartherthatprimaryandsecondaryobjectives of design during investigators, the FDAand between negotiated dependent onestablishmentofprimaryandsecondaryobjectives Oral lectureabstracts Acta DermVenereol Suppl220 17 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta are mainlyworninanextended or constantwearmodeof24h/7d lenses The 2006. since used were 16mm to 11 between diamter from extremehighoxygenpermeable hardmaterialwithoverall permeable anddepositresistant soft silicone-hydrogelmaterialor tice bandage contactlensesmade out ofextremehighoxygen new formedneovascularisation andscartissue.Inclinicalprac They wereabletorestorevisionanddicreasedtheoccuranceof pain sensation, exessive tearing and chronic ocular inflammation. lenses haveshowntobe more effctive inpermanentlyreducing contact bandage sepcialized cases, severe more in However, employed. being are creams and drops eye moisturizing cases, attempt toreducetheoccurranceoftheseerosionsinlesssevere and reduced vision with an incidence rate of about 40-51%. As an is often affected by recurrent and painful corneal erosions, scarring The ocular surface ofmainly dystrophic and junctional EB patients AG, Bern,Switzerland Department ofspecialized Contact Lenses andOptometry, eyeness Michael Baertschi EPIDERMOLYSIS BULLOSA EYE: THERAPEUTIC CONTACT LENSESFOR OP61 improving thecareofpatientswiththisskincondition. keyfor is andreferencecenters collaboration amongresearch condition, each patient presents an unique challenge. International to preventsecondarydamage. As EBisarareandhighlyvariable covered be should abnormality,teeth enamel the of severity the cause tooth sensitivity, attrition or failure to erupt. Depending on can This enamel. hypoplastic severely to fissures and pits form EB: patients present with Junctional generalized enamel in hypoplasia, varying challenges Specific comfort. and aesthetics ning, improving patient’s qualityoflifethroughenhancedoralfunctio RDEB, in rate success osseointegration 1-year 98.6% a have access topreventivecaremightbeedentulous.Dentalimplants plasty toreleasethelip.(3) Adults withRDEBwhohavenothad removing hooks from brackets if they cause ulcers, or vestibulo as such adaptations, some need might RDEB generalized severe tion and fixed orthodontics in permanentdentition. Patientswith specific analysis considering serial extractions during mixed denti and patients age. (2) Tooth crowdingcan be managed by patient exercises and stricture release surgery, depending on the severity with approached be can which Microstomia, (1) include: RDEB arrest strategies to minimize dental disease. Specific challenges in hes, fissure sealants and a variety of remineralization and carries instructions aided by plaque disclosing solutions, fluoride varnis andoralhygiene earlydiagnosis ulcers; andtheclinicianprovides oral manage to alternatives and scheme fluoride specific patient toothbrushes, appropriate with hygiene oral to commits family prevention andpatient-clinicianpartnership. The patientandhis and continuous dental care throughout life focused on education, referral early on based is program care oral The 2016. in fected of affectedteeth 10.2 af from teeth decreased 1.8 caries to 2006 in severity years, 6 to 0 aged (RDEB) Bullosa Epidermolysis looked after. InthecohortofpatientswithRecessiveDystrophic are EB with living people ̴250 where Diseases, Rare for Center clinical experienceoftheUniversidaddeChileDentalReference published later in 2020. This conference was based on the 15-year New evidencehasbecomeavailableandarevisedversionwillbe 2012. in published was EB with living people for Care Health The first Guideline commissioned by Debra International on Oral Chile, Santiago,Chile Special Care DentistryUnit,Faculty ofDentistry, Universidadde Susanne MarieKrämer EPIDERMOLYSIS BULLOSA) ORAL HEALTH (DENTAL TREATMENT IN OP60 18 EB2020 1 st WorldCongressonEpidermolysisBullosa ------ANEMIA INEB OP63 continuous nutritionalsupplementationinRDEB. 3) and years, <2 intervention nutritional starting 2) follow-up, clinical for charts growth disease-specific of use and months 3 every EB with children Measuring 1) given: are management patient for recommendations following the conclusion, In tion. inflamma and zinc, and D vitamin of deficiencies albumin, low with the amount of collagen VII in the skin, presence of anaemia, of weight gain beginswithin the secondyearoflifeandcorrelates prognostic measure forgrowthdevelopment in RDEB. Stagnation children with recessive dystrophic EB (RDEB). Weight is the best obesity.This talkfocussesontherecentlydescribedgrowthpatternsof for risk at are simplex EB with individuals while EB, these, failure to thrive is a major complication in severe dystrophic taneous manifestationsarecommoninseveresubtypes. Among Despite epidermolysis bullosa (EB) being a skin disease, extracu burg Department ofDermatology, Medical Center – University of Frei- Antonia Reimer BULLOSA GROWTH PATTERNS INEPIDERMOLYSIS OP62 No abstractsupplied Guy’s &St.Thomas’ NHSFoundation Trust, London,UK Catina Bernardis SURGERY FORSCC OP65 No abstractsupplied Great Ormond Street Hospital NHS Foundation Trust, London, UK Gill Smith HAND SURGERY –MANAGEMENT STRATEGIES OP64 of anemiainEBpatients. Statements address diagnosis, monitoring, treatment and outcomes in the process and 20 statements were approved for this guideline. guidelines were created. A modified Delphi methodology was used ternational initiative to create clinical practice guidelines, anemia interventions suchasbloodtransfusions. As partoftheDebraIn giving oralorintravenousironsupplementsconsideringother improve nutritional status, decrease inflammatory state, as well as factors need to be addressed, like putting in place interventions to anemia inEBisitstreatment.Foroptimalmanagementmultiple interpreting bloodtestresults. The secondchallengefacedwith special considerationsthatneedtobetakenintoaccountwhen only difficult to obtain blood from EB patients, but also there are Diagnosing anemia in EBpatients may be challenging as it is not mation, among many others, making this a multifactorial problem. wounds, decreased iron absorption, decreased oral intake, inflam from loss blood like EB, in anemia to lead that factors many are patients,anemia. There sufferfrom EB, of forms severe with particularly of 100% to up report manuscripts few but scarce, is is higherthaninthegeneralpopulation.Literatureonthistopic dermolysis bullosa(EB).PrevalenceofanemiainEBpatients Anemia isacommonproblemencounteredinpatientswithepi diatrics, UniversityofToronto, Canada Hospital forSick Children, Toronto, Canada, DepartmentofPe- Irene Lara-Corrales increased thepatient’s qualityoflifesustainablyandeffectively. consequently and lesions corneal superficial recurrent minimize to helpful are lenses contact protective of use The 24h/30d. or - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV surgeries, andnivolumab. complex therapy, radiation cetuximab, with treated was which SCC, metastatic and primary with presentation initial her since limited. This woman with RDEB has survived for over five years this presentation. As this is a single case report, generalizability is patient hasbeenstableoff therapyforfourmonthsatthetime of over threeyearsandwaswell-toleratedexceptforfatigue. The suggested remissionoftheSCC.Nivolumabwascontinuedfor tumors occurred. Subsequent clinical examinations and imaging PD-1 inhibitor nivolumab was started, and rapid involution of the fecting hercervicallymphnodesandchestwallwasfound. The amputation of the left arm. Two months later, metastatic SCC af left humerusduetometastaticSCC.Sheunderwentforequarter Six months later, the patient sustained a pathologic fracture of the plicated bylymphedema andpoorhealing ofthe axillary incision. the elbow amputation and lymph node dissection, which were com currence ofthetumorwasapparent. The patient underwent below improvement was seen, but six months after treatment ended, re forearm andaxilla (45 Gy over15 fractions) weregiven.Marked the to therapy radiation and cycles 5 x cetuximab and refused, SCC intheaxillarylymphnodesonaffected side.Surgery was to poorlydifferentiated SCCinthe othertwo. Workup revealed well tomoderatelydifferentiated SCC inoneareaandmoderate suspicion ofsquamouscellcarcinoma(SCC).Pathologyshowed clinical the confirmed tumor the of biopsies Three forearm. left bullosa (RDEB)presentedwitharapidlyenlarging tumoronher epidermolysis dystrophic recessive with woman 40-year-old A Colorado, USA School ofMedicine,Children’sUniversity ofColorado Hospital Anna Bruckner METASTATIC SCCMANAGED WITH NIVOLUMAB REPORT:RDEB AND CASE WITH AWOMAN OP67 tised bypodiatristsshowpositiveoutcomes. Evidence hereislimitedbutseveralinterventionscurrentlyprac mobility; andfusionoftoes(Pseudosyndactyly). gement ofdystrophicnails;hyperkeratosis(Callus);maintaining exploring themostsuitablefootwearandhosieryforEB;Mana management. These includedblisteringand woundmanagement; main areaswhichthecommunityindicatedasaprioritytofoot an EBcommunity international survey theoutcomes indicated six professionals, patient representatives and lay reviewers. Following care health other experts, of panel a by process review external methodology wasused. The resultingdocumentwentthroughan day. The Scottish Intercollegiate Guidelines Network (SIGN) present to 1979 as early as identified were treatment podiatric to with Epidermolysis bullosa (EB), was undertaken. A​ systematic literaturereviewrelatingtothepodiatriccareofpatients delines for people and their families and carers, living with EB. A and users, with an evidence based set of current best practice gui on experienceandexpertopinion. To provideserviceproviders podiatric careofEBandmanagementdecisionsareusuallybased of thedisorder. Furthermorethereisadearthofevidenceregarding but becauseofitsraritymanypodiatristshavelimitedknowledge care podiatric specialised requires EB 2012). Khan 2010; (Khan nail dystrophy or structural abnormality affecting foot positioning, tric manifestations, including blistering, hyperkeratosis, flat feet, UK 2018). Ninety percent of EB patients have one or more podia presenting asblisteringoftheskinfromminortrauma(DEBRA typically disorders, fragility skin heritable rare of group a is EB University CollegeLondonHospitalsNHSFoundationTrust Hospital forIntegratedMedicine, Marigold Clinic,RoyalLondon Tariq Khan PODIATRY OP66 rticles relating ------of EBandahighqualitylife. surgery thepatientisincomplete remission withimprovedsigns college, return back to work and start a family. 15 years after the including restagingintheEBCenter. Shewasabletograduate years shefollowedtherecommendationofregularcheck-ups bearing usingspeciallymanufacturedprosthesis.Overthenext in thehealingofstumpandpatientstartedearlyweight year fromthediagnosis. There wereobservednocomplications below thekneelegamputationwhichwasexecutedwithinhalfa in cooperationwithEBphysiatristpreparedthepatientfor pain and strongodoreventuallyagreedtoit. excessive The EBplasticsurgeon for but first, at surgery the refused patient The skin oftheuppercalfandclosecooperationwithaprosthetic. choice. Advantages favoringthistreatmentwerenon-blistering mended by the multidisciplinary EB team as the treatment of ruled outmetastaticdisease. Amputation ofthelimbwasrecom overlapping themargins. Stagingandevaluationoflymphnodes the wound on the foot revealedsquamous cell carcinoma (SCC) of excision dysphagia. Total and fingers the of contraction mild with pruritus, as well as mouth and teeth lesions, onychodystrophy, hemorrhagic vesicles, crusts, atrophic erosions, lesions and including depigmentation affections skin diffuse by affected was she had achronicwoundontherightfootlastingforoveryearand National EBCenterinBrnoaftertenyearsattheageof28.She she voluntarily interrupted the regular check-ups and visited the adolescence In p.(Gly2049Glu)). p.(?)/c.6146G>A (c.425A>G firmed by genetic analysis with the finding of COL7A1 mutations the electronmicroscopyexaminationofskinandwaslatercon Hospital inBrnosincebirth. The initialdiagnosiswasbasedon treated attheDepartmentofPediatricDermatologyinChildren’s A 43-year-old womanwithRDEB AR generalizedseverewas University HospitalBrno,CzechRepublic Pavel Rotschein RESPONSE INRDEB AR GENERALIZEDFORM CASE REPORT: SCCMANAGEMENT AND OP68 investigate asublinguallyadministered CBM-oilinthesettingof DEBRAwill a grant, awarded being center,after EB Groningen use ofCBMsinEBorderto identifyresearchavenues. The Groningen (NL)EBcenterswill collectinternationaldataonthe daily lifeinEB. A collaborationbetweentheStanford(US)and the roletheymayplayintreatment ofthesymptomsaffecting repurposed treatments, such as CBMs – and objectively scrutinize ten inadequate, there there is an imperative to investigate novel or cannabidiol), respectively. As symptomatic treatment for EB is of derived cannabinoids)andtopicallyappliedCBMs(comprising oil (comprising tetrahydrocannabinol and cannabidiol, both plant healing inpatientstreatedwithsublinguallyadministeredCBM- wound and pruritus pain, improved described States United the population isemerging. Two caseseriesin patient The Netherlandsand EB the in CBM-use anecdotal and aetiologies, various CBMs ontop-downsymptomssuchaspainandpruritusfrom of CBMtherapies.Researchhaslargely focusedontheeffect of ligands, and provides a basis to cannabinoid-like understanding the potential bind effect which receptors, of abundance an tains and disease. The endocannabinoid systemfoundinhumanscon growing understandingoftheendocannabinoidsysteminhealth our to regard with realms clinical and scientific the in attention Cannabinoid-based medicines (CBMs)are gaining increasing versity MedicalCenterofGroningen, TheNetherlands Center forBlistering Diseases,DepartmentofDermatology, Uni- Nicholas Schräder PRURITUS INEB FOR PAINMEDICINES CANNABINOID-BASED AND OP69 Oral lectureabstracts Acta DermVenereol Suppl220 19 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta new, supportstrategies. fronted with new challenges and must adapt their old, or develop con continually are child’sparents the development, Regarding into educational workshops and translated intoother languages. de/downloads/). In the future those materials will be embedded English and Italian German, free of in charge (https://kinderpalliativzentrum. downloaded be can information helpful other as www.deutsches-kinderschmerzzentrum.de/en/eb-video/) aswell movie with English subtitles (Movie with English subtitles (https:// materials havebeendevelopedtosupportparents. An education are keyissueforparentsandaffected children.Severaleducation change andtheuseofpsychologicaltechnicstosupportchild children. The use of dressing materials in the context of a dressing Especially thedailydressingchangeishighlybothersomefor its treatmentandvariousmedicalprocedures. Pain in Epidermolysis bullosa (EB) is caused by the disease itself, decke University, FacultyofHealth,SchoolMedicine,Germany Children`s PainTherapyandPaediatricPalliativeCare Witten/Her Boris Zernikow PREVENTION AND TREATMENT OF PAIN OP71 neuropathic painsymptoms. pathy inRDEBpatientswhichwillhopefullyleadtoarelief neuro fibre small of treatment for targets identify to us allow of neurotrophinsinaxonalregenerationafterskindamagewill do notregeneratefollowingskindamage.Investigatingtherole not secretetheseneurotrophinsandtheirintraepidermalaxons do patients RDEB from keratinocytes However, regeneration. was showntosecreteneurotrophicfactorsthatinducesnerve severed andsuffer degeneration. The skinofhealthyvolunteers regeneration. In summary, after skin lesion, epidermal axons are medium fromRDEBkeratinocyteswasunabletoinduceaxonal conditioned while neurons, sensory rat in regeneration axonal keratinocytes from healthy volunteers induced an increase in RDEB keratinocytesdonot.Conditionedmediumfromprimary healthy volunteerssecreteNGFafteraninvitro scratchlesionbut using ELISA. We alsoobservedthatprimarykeratinocytesfrom results these Weconfirming patients. are RDEB in abolished is the skin of healthy volunteers after skin lesion, but this response found that there is an increase in NGF and GDNF transcripts in to treat sensory neurons. Axon regeneration was measured. We was testedforneurotrophinsecretionafterinjuryandwereused from patientsandcontrols.Conditionedmediathelatest grown investigated usingqPCRand WB. Ratsensoryneuronswere RDEB adult patients and matched controls. Neurotrophins were A 3mm punch biopsy was obtained at 10 days after skin lesion in rotrophic factorsinepidermalaxonalregenerationafterinjury. neu of role the on emphasis special with neuropathy fibre small understand themechanismsbehindthisRDEB-inducedpainful to neuropathic pain and itch (Brain 2017). In this study we aim to RDEB patientshaveadecreasedepidermalinnervationthatleads transduce pain from the epidermis. We thatrecently showed and border dermo-epidermal the cross that fibres unmyelinated small/ and dermis, the in mechanosensors innervate that fibres Skin innervationconsistsoflarge diameter/highlymyelinated Pontificia UniversidadCatolicadeChile Margarita Calvo,MD,MSc,PhD RDEB SECONDARY SMALL FIBRENEUROPATHY IN OP70 quality oflifeinpatientswithEB. a controlledclinicaltrialwiththeaimtoobjectifyitseffect on 20 in vitro atthesametimeasprimaryhumankeratinocytes EB2020 1 st WorldCongressonEpidermolysisBullosa - - - - repurposed foritchtreatmentinEBpatientswithchronicpruri been have agents therapeutic However,novel gabapentinoids). antihistamines,oral non-sedating or sedating emollients, roids, as atopicdermatitisorprurigo(e.g.topicalglucocorticoste also usedinthecontextofotherchronicpruriticdiseasessuch therapies “historical” or established with performed been has EB with adults and children in treatment pruritus decades, For mediators. other of multitude a and proteases neuropeptides, are transmitted by extensive tissue crosstalk through cytokines, nerves aswellspinalcordandbraincells. Their itchsignals EB pruritogenesis involves keratinocytes, immune cells, sensory gic and, far less frequently, histaminergic pathways. Additionally, pruritus inEBisverycomplexmostlyinvolvingnon-histaminer suffering fromthe highest itch burden. The pathophysiologyof with recessivedystrophicEBseemtobemostseverelyaffected patients note, Of duration. and frequency severity, itch higher moderate in most patients, other forms of EB are associated with EB subtype. Whereas pruritusscoresinEBsimplexaremildto to according significantly differ profiles itch However, areas. certain bodysitessuchasthelegsandfeetareitchiestaffected some complications. In all EB subtypes, healing wounds and/or in whomithasevenbeendescribedasoneofthemostbother pruritus alsooccursinpatientswithepidermolysisbullosa(EB) Defined as the unpleasant sensation leading to the need to scratch, Children’s Hospital Auf derBult,Hannover, Germany Hagen Ott PRURITUS INEPIDERMOLYSIS BULLOSA OP72 hospital without a dedicated space specifically designed for the for designed specifically space dedicated a without hospital clinics hadbeenhostedinmany different areasthroughout the needs; clinical variable very with patients) 480 c. (currently were challengesaroundproviding careforalarge EBcohort Historically,there settings. inpatient and outpatient both in EB provides it England, multidisciplinary (MD)careforindividualswithallformsof in centres EB adult 2 of one as Service adult EBserviceformanyyears.FundedbytheNationalHealth Guy’s and St Thomas’ NHSFoundation Trust has hosted an Foundation Trust, London St John’s Institute ofDermatology, Guy’s andSt.Thomas’ NHS Jemima Mellerio (GSTT) RAREDISEASECENTRE MULTIDISCIPLINARY TEAM BEST PRACTICE OP73 tient numbersareurgently needed. controlled investigationsoftheseagentsincludingsizeablepa in preliminary case studies or small clinical trials. Hence, further lesions, novel and promising therapeutic agents have been used known tohavelittleimpactonitchintensityandpruriticskin in allEBsubtypes. While established therapeuticstrategiesare represents a still undertreated, yet highly significant complication summary,pruritusIn pruriginosa. EB dystrophic with adult an has beenreportedtoreducepruritusandpruriticskinlesionsin pruritus, uremic and cholestatic in off-label used previously Naltrexone, antagonist receptor μ-opioid oral the Finally, EB. itch severity and a good safety profile in patients with dystrophic randomized trial revealing small, but clinically relevant effects on first a in investigated been has Serlopitant antagonist receptor Neurokinin-1 oral the Likewise, pruriginosa. EB dystrophic in successfully been used to reduce itch and prurigo-like skin lesions has dermatitis, atopic of treatment subcutaneous for approved (Dupilumab) antibody IgG4 monoclonal humanized a reover, Mo simplex. EB severe generalized in pruritus inflammatory alleviate to shown been recently has psoriasis, of treatment for licensed inhibitor phosphodiesterase-4 oral an tus. Apremilast, ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV are limitedparticularlyinrarediseases likeEB. individual patients. This isveryusefulwherestate funding andphilanthropy in interventions specific to funds raise to used was of traveltoBangaloreforregularcare.Crowdsourcingstrategies conduct anEBclinicthroughtelemedicine. This reducedthecosts of referral;ourteamwouldliaisewiththereferringclinicianto It is https://chgregistryapp.appspot.com/register/chg upon receipt dically senttopediatriciansanddermatologistsseekreferral. model toreachoutandfar. The followinglinkwasperio opening issues and finger splinting. Wemouth created afor hub-and-spokes materials available locally chose we Likewise, best. dressings andallowedthepatientstochooseonethatsuited feteria approach. We distributedEBkitswithsamplesofavailable percent. 50 Woundby cost ca a on based was management care testing. This approach costed about $250, which is a reduction of genetic then and findings mapping antigen immunofluorescence care management. targetedApproach todiagnosiswas onthe based focus onestablishingdiagnosisthesubtypeofEBandwound doctors andadhocpatientcaretomulti-disciplinaryclinicswitha these patients. The journeybeganwithreferralsfromindividual by thegovernmentposesgreatchallengesinprovidingcarefor heterogeneity, huge land area and limited funding for rare diseases Epidermolysis bullosa is common in India. However, population Centre forHuman Genetics,ManipalHospital,Bangalore Ravi Hiremagalore SETTING MANAGING EBIN A RESOURCELIMITED OP74 provision ofaonestopshopexperiencewherepossiblearekey. the with need patient around flexible is that design clinic and with other similar services, patient engagement from the outset, forces join to opportunities taking However, challenges. many rare, lifelong, complex medical conditions such as EB can present Establishing abespokecentreforthecareofindividualswith especially forbiopsiesofpotentialskincancerswithoutdelay. patient travel. Ad hoc reviews are an essential part of the service, podiatry clinicsandnewlyestablishedSkypetosaveon clinics runningweekly. Moving to theRDChasled to weekly EB nurse-led additional with clinic, each patients 30-40 sees clinic outpatient monthly a needs, complex less with stopthose For one shop. a as available tests other and infusions tests, blood enabling access to the full MD team in one clinic with biopsies, clinics run monthly for individuals with the highest level of need, different specialiststhatneedtobeseen.FullMDandmini-MD the and need patient on depending run, that clinics of types the to the adult EB service. The RDC has enabled great flexibility in first of its kind for adults and children in the UK, opened its doors to this concept. In November 2017, the Rare Diseases Centre, the calm, contemplative space for patients and carers has been central to beablesocialisewithotherswaskey. A gardenprovidinga relaxing and non-clinical as possible, also highlighting the need for allstakeholdergroups. An emphasisonmakingthespaceas element inthedesignof the space with practicalconsiderations services withmanycommonalities.Patientengagementwasakey space, as well as enabling a combined sense of purpose between and deliverable economically and in terms of maximising clinical with other rare disease services meant that the project was feasible forces Joining completed. refurbishment and identified space a secured, was funding before iterations various and years many the idea of specific clinical space for the GSTT EB service took 2009, in initially Conceived mind. in EB with people of needs - - No abstractsupplied Thomas JeffersonUniversity, Philadelphia,USA Bahar Dasgeb EB AND COMPLEXSKINCANCERCLINIC EB-ASSOCIATED SCC: THE JEFFERSON ADULT OP76 2. Warshaw EM, Hillman YJ, Greer NL, Hagel EM, MacDonald R, Rutks IR, Wilt TJ teledermatology interactive Live M. Otten M, Augustin TM, V,Klein Andrees 1. References ning aliveinteractivevideoconferencingclinicinEB. for bothpatientandhospitals. We discussourexperience ofrun care, reducing patient travel times and delivering cost efficiencies tospecialist acompellingformatforimprovingaccess EB presents delivered in theUK.Use of teledermatologyin the managementof is startingtotransformthewayinwhichmanyservicesarebeing Since the 1990’s, this model of care has gradually gained pace, and and treat patients remotely, using telecommunications technology. Telemedicine allows healthcare professionals to assess, diagnose Foundation Trust, StThomas’ Hospital,London,UK St John’s Institute of Dermatology, Guy’s andSt Thomas’ NHS Danielle Greenblatt TELEMEDICINE OP75 that have to be mastered for: the best self-management, prevention 2: a patient centred approach. It means to list all the competencies -Step environment; psychosocial life, daily expectations, needs, patient: each for analyse to questionnaire a of help the with ans 4 steps: -Step 1: the educational diagnosis for each patient: it me Ministry, with an involvement of patients. The program includes set up a concise program for EB patients , certified by thehas Health 2009, since TPE in graduated members) staff paramedical and medical (11 team professional multi a (MAGEC-Necker), centre our In life. of period each program; to adapted tools, 3-educational concise 2-a TPE; in trained team 1- are: needs TPE characteristics. emotional sociocultural, familial, own (her) his with person the also and patient, the disease, the understand: to and patients/families. The tasksforthehealthcareprovidersare is alsoasynergistic andreciprocaleducationbetweencaregivers do (cognitive dimension), how to be (emotional dimension). to TPE (how approach patient-based constant a with complications, of therapeutic recommendations; -avoid/decrease relapses and understanding the autonomy, the life, of quality the of impro vement sustainable a permit - to: are objectives TPE EB. their strategy tohelpthepatientsliveandnotonlysurvivewith tsunami. In our experience, TPE is the most rigorous and efficient true “a traumatism, familial intense an is neonate EB an of birth The manage. regularly are patients EB 400 than More period. Adult until birth from patients of care take we patients, EB for centre our In Organization). Health (World terms financial and diseases to manage their illness and yields benefits in both health Education (TPE)enablespeoplewithchronic Therapeutic Patient France dermatoses (MAGEC),Hôpital Necker-Enfants Malades, Paris Department of Dermatology, French national centre forgeno- Christine Bodemer EDUCATION PROGRAMMES OP77 review. J Am Acad Dermatol.2011 Apr;64(4):759-72. . Teledermatology for diagnosis and management of skin conditions: a systematic 2019. doi:10.1111/jdv.16070. compared toin-personcare-asystematicreview. JEur Acad Dermatol Venereol. Oral lectureabstracts Acta DermVenereol Suppl220 21 - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta for the overall pathogenicity/virulence of the bacteria, has been has bacteria, the of pathogenicity/virulence overall the for communication system (quorum sensing, QS), which is important ment strategies are urgently called for. Interfering with the bacterial ever-increasing problem of antibiotic resistance, alternative treat wounds are typically treated with antibiotics. However, due to the and suffers from a high pro-inflammatory status. Infections of EB Chronic EBwoundsaregenerallycolonizedbymicroorganisms Care AB grenska Academy, UniversityofGothenburg &Mölnlycke Health Department ofBiomaterials,Institute of Clinical Sciences, Sahl- Erik Gerner BACTERIAL COMMUNICATION TARGETING WOUND INFECTION–DISRUPTING A POTENTIAL NEW THERAPEUTIC APPROACH OP80 No abstractsupplied EB Research Partnership,NewYork, USA Michael Hund INNOVATION INPATIENT DATA PLATFORMS OP79 data andtransferoftotheInternationalRegistry. Development ofStandardOperatingProceduresfortheinput national dataset would be meaningless. 3) GDPR compliance. 4) not agreedthentheoutputfromanyanalysisofacommoninter are definitions If variables. agreed the of each for exercise tion each oftheparticipatingcentres.2)Undertakeadataharmonisa 1) Finalise the minimal dataset thatis feasible to becollectedfrom tive Committee with the following agenda items to be agreed upon: Actions: Convene a meeting of the International Registry Execu be carriedbyeachcentrewishingtotakeadvantageofthisoffer. considerable development costs. Localisation costs would have to the coretechnologyforInternationalRegistry. This willsave National Registryavailabletoothercountriesandas will make thecoretechnologythattheyhavedevelopedfortheirown Ireland funding, of lack the to Due costs. operational and that coverstheplatformdevelopmentandongoingmaintenance Committee. A registry needs to be sustainable, it requires funding in aminimalcommondatasetandtheformationofRegistry resulted (2017) Salzburg and (2016) Dublin in meetings initial updated andisavailablefromDebraInternational.Output sion for a number of years. The “State of Play” document has been The concept of an International EB Registry has been under discus National &InternationalSkinRegistrySolutionsCLG Godfrey Fletcher INTERNATIONAL EBREGISTRY OP78 disease inallitsdimensions. and expectationsoftheircolleaguestobetterunderstandthe techniques the in themselves “educate” to providers care the led has management, paramedical and medical multidisciplinary patients’the of areas necessary the all therefore, and, experience tion withamutualaid;thedesignofcollectivetoolcoveringall context of a program encourages speech, allows a break in isola trust betweenpatients/familiesandcaregiversisstrengthened;the group of ages. In our experience, TPE is a gradual experience: the assessment. Educationtoolshavebeencreatedadaptedtoeach The objectiveistoadjusttheprogramonbasisofcontinuous involvement; Step 4: the evaluation of the acquired competencies. systemic the concern -2 nursing, and wounds the concern 10 to -8 genetic, the forms, EB the skin, the concerns -2 offered: are tical TPE programforeachpatient.12sessions(1hoursession) prac a of implementation -Step3: adaptation; psychosocial a for of avoidable complications, secure lifestyle, organized awareness 22 EB2020 1 st WorldCongressonEpidermolysisBullosa ------Amryt PharmaceuticalsDAC,Dublin,Ireland Mark Sumeray OLEOGEL-S10 AND AP103 WITH PROGRESS TO WOUND HEALINGINEB– AN UPDATE ON DEVELOPMENTOF TWO TOPICAL APPROACHES OP81 anti-infectious agentusinginvivoinfectionmodels. factor NF-κB, which encourages further evaluation of NaSa as an survival and reduced activity of the pro-inflammatory transcription fibroblast improved production, toxin bacterial less in resulting activity, anti-QS NaSa on proof-of-concept the presents work stimulated monocytes resulted in decreased NF-κB activity. This NaSa. Addition ofNaSatodifferentiated andlipopolysaccharide- without cultures for seen was opposite the whereas fibroblasts, bacterial cultures with NaSa were not toxic towards human dermal infections, without inhibiting bacterial growth. Supernatants from binding siderophores, both important factors in persistent wound NaSa resultedinreducedlevelsofthetoxinpyocyaninandiron- gulating a subset of important virulence factors. Treatment with sation which can negatively impact wound-healing, the quality the wound-healing, impact negatively can which sation coloni bacterial in result may fragility skin EB, of forms all In Flen Health Gilles Brackman ON TOPICAL WOUNDTREATMENTSELECTION THE IMPACT OF ANTIMICROBIAL RESISTANCE OP82 also addresstheunderlyingcauseinhope of a potentialcure. to developarangeoftreatmentsnotonlyhelpmanageEBbut development ofnewtreatments for EB. Amryt Pharmaareaiming are the cornerstones of the commitment of Amryt Pharma to the losa were there is a mutation in COL7A1. Oleogel-S10 and AP103 potential asatherapyforrecessivedystrophicepidermolysisbul applications. topical has via AP103 collagen type VII functional fully express to bullosa. cells epidermolysis skin enables AP103 dystrophic recessive of treatment the for therapy,AP103, gene cacy data in 2020. Amryt Pharma is also investigating a non-viral effi provide will EASE that are Expectations 03068780). NCT 2016-002066-32; No. (EudraCT EASE as known syndrome), kindler and EB dystrophic junctional, (with patients EB ~250 in study III phase global largest the in assessed being is and 2017) studied in an initial proof-of-concept study in EB (Schwieger-Briel with split-thickness graft wounds and burns. Oleogel-S10 has been patients in healing wound accelerated shown have Oleogel-S10 of studies Clinical transglutaminases. and 10 keratin involucrin, differentiation into terminal phase skin cells via upregulation of ratinocyte migration via Rho-activated kinases, and keratinocyte ke promotes TE addition, In cyclooxygenase. and IL-8 6, (IL) portant tothewoundhealingprocess. These includeInterleukin im mediators inflammatory of upregulation transient cause that activities have to known already is extract the but investigation, treatment forepidermolysisbullosa. The modeofactionisunder and erythrodiol. apotential gelas developing this is Pharma Amryt ting ofbetulin(72%–88%),betulinicacid,lupeol,oleanolicacid sunflower oil with triterpene extract (TE) from birch bark consis Oleogel-S10 (AP101) is a specially formulated gel preparation of Birch barkhaslongbeenknowntohavewoundhealingproperties. with three interconnected QS systems in P. aeruginosa, each re P.each in aeruginosa, systems QS interconnected three with was found thatNaSa effectively interferedtoa different extent or treatmentofwoundsinfectedbyPseudomonasaeruginosa.It salicylate (NaSa) as a QS inhibitor to be used in the prevention The aimofthisstudywastoinvitro evaluatetheactivityofsodium to betterperformitsroleinclearingorpreventingtheinfection. is tomakebacterialesspathogenicallowingtheimmunesystem proposed as an alternative option. The target of such treatment ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV reduces the risk of periwound maceration. Hydrofiber maceration. periwound of risk the reduces also dressing the in fluid the retaining by but bio-burden the of the dressing. This Technology not only supports management thus notonlyinhibitreproductionbutkillbacterialockedwithin attributes are protecting the peri-wound skin, avoiding skin strip the correct dressing for managementof EB wounds. The 4 key of selection of guidance general offers Denyier¹ fit? dressings of the bio-burden. Characteristics of Hydrofiber of Characteristics bio-burden. the of management optimal supporting again proliferate, may bacteria wound surface and the dressing where fluid may accumulate and This meansthatthereisnoorverylittledeadspacebetweenthe logy has the ability to closely ‘micro-contour’ to the wound bed. Hydrofiber producing. the dressing. This bacteriostaticactionstopsbacteriafromre within held and trapped are enzymes), and cells inflammatory (bacteria, contents its and fluid the swell fibers the As exudate. fluid/ wound retain importantly most and absorb to dressing the of ability in’ the ‘Locks is benefits. patient and management dressings to ‘lock in’, ‘contour’ & ‘respond’ offers optimal wound the in dressings. of family Hydrofiber® AQUACEL® of Ability Technology isderivedfromahighpuritycelluloseandfound Hydrofiber® technology. responsive and well-constructed a by underpinned be to need dressings wound challenge, this meet To management. exudate and bio-burden the addressing ping, of productsandpersonalpreference availability exudate, of levels colonisation, critical or infection of presence EB, of type the to specific is management Dressing status, anaemia, pain and pruritus…) and the fragility of the skin. nutritional poor defect, genetic (underlying morbidities co tiple Wound management in EB is complex as it is influenced by mul ConvaTec, UK Rachel Torkington-Stokes WOUND MANAGEMENT THE ROLEOF HYDROFIBER® DRESSINGSINEB 0P83 glucose-oxidase, lactoperoxidaseandguaiacol. resistance towards the antimicrobial enzyme-system consisting of that pathogens commonly reported to infect wounds do not evolve for theirpotentialselectionofresistance.Ourresultsindicate agents usedinwoundcareshouldbeassessedatanearlystage resistance inwoundcare. All systemicandtopicalantimicrobial important tooltolimitandcontrolthedevelopmentofmicrobial ning a rational use of systemic and topical antimicrobials is an repeated treatments with the antimicrobial enzyme-system. Defi expected tobeobservedbetweenpopulationsexposedoneor >50 cycles. Additionally, no significant phenotypic changes were in thenumberofpersistercellswereobservedduringany or MBC MIC, in changes No enzyme-system. antimicrobial the micro-organisms whenexposedtosub-optimalconcentrationsof the of any in observed were susceptibility in changes no ticles, analysis. Incontrasttowhatisobservedfore.g.Silvernanopar genomic and phenotypic microbiological, different applying guaiacol and lactoperoxidase glucose-oxidase, of consisting development towardsapatented antimicrobial enzyme-system development. In this study, we investigated the potential of AMR to begiventhepotentialofantimicrobialresistance(AMR) infected wounds and wounds at risk of infection, attention needs of lifeandresultinincreasedhealthcarecosts. When managing benefits Hydrofiber case reportswerepresentedto illustrate thewoundandpatient Several care. wound and skin dictates EB of type the accepted, widely is stripping.As skin avoiding hence tissue, formed newly debridement andsupportsthehealing processwithoutdamaging autolytic aids environment, wound moist a maintains helps gel wound conditionsinitiatestheformationofacohesivegel. The ® Technology canoffer. ® dressingswithsilverarebacteriocidal 1 . Where do Hydrofiber® do Where . ® to ‘respond’to to ® Techno ------2010s saw an increasing number of DEBRAs established throug been well represented since the 1980s and 1990s. The 2000s and have and North Australasia America, Europe, world. the around countries in groups national 50 than more of establishment the international in scope. Over the past 40 plus years, we have seen inspirational origins, DEBRA has grown significantly and is now to fund medical research into EB. From those humble, brave and for the benefit of those with the condition and their families, and EB in, interest and of, knowledge stimulate to were charity the of aims original The away. passed Debra founded, was charity support group. Sadly, on the 21 patient EB first world’s the – formed being UK DEBRA to led meeting, which was held in Manchester. This was a meeting that meeting forparentsofchildrenwithEB.78peopleattendedthe zines, radio stations, celebrities, and hospitals to organise the first unless sheandotherparentstookaction.Phylliswrotetomaga dened thatnothinghadchangedin15years–andwould baby whohadbeenbornwithEB.Phylliswasshockedandsad woman who wanted help and advice followingthe birth of her a by contacted was Phyllis mum her 15, was Debra when 1978, dressings. Yearscotton Debra’susing treat skin later,in to ways until shedied.Phyllisignoredthisadviceandinsteadlookedfor could be done for Debra and to take her home and look after her about EB; Her mum, Phyllis, was told that there was nothing that In 1963, a girl called Debra, with EB, was born. Little was known DEBRA, Spain Evanina Morcillo Makow HISTORY – A40-YEAR WORLD THE DEBRAS AROUND OP84 1. DenyierJ- Wound managementinepidermolysisbullosa;EWMA JOURNAL Reference: have been treated with ex vivo COL7A1 treated autologous per patient COL7A1 treatedautologousepidermal monolayergrafts(6 ding 7pediatricpatients.adults havebeentreatedwithexvivo inclu far, so Stanford at therapy gene with treated been have the molecularcorrectionofRDEB.Intotal26RDEBpatients clinical trialsemployingseveralpromisingnewtechniquesin Our group has been active in studying a group of early phase Stanford UniversitySchoolofMedicine,Stanford CA USA Department ofDermatologyandProgram inEpithelial Biology, M. PeterMarinkovich RESEARCH UPDATE (GENE AND PROTEIN) OP87 No abstractsupplied King’s CollegeLondon,UK Su Lwin RESEARCH UPDATE (CELL THERAPY) OP86 No abstractsupplied Debra of America, NewYork, USA Brett Kopelan/ COLLABORATION DEBRA INTERNATIONAL/ CO-ORDINATION AND OP85 development oftheinternationalDEBRA groupnetwork. what this new decade, and indeed the next 40 years, holds for the seeing to forward look we year, per established group new one of average an With America. South and Central and Asia, hout 2016 VOL 16NO143 = 42 graftstotal).5adultsandone pediatricpatient Jimmy Fearon st of November 1978, the year the Oral lectureabstracts Acta DermVenereol Suppl220 23 - - - -

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta therapies; recent research into the pathogenesis of these cancers is have limited benefit and highlight a desperate need for improved years (Fine et al. 2009; Kim et al 2018). Current treatments often 2.5-5 of SCC first of diagnosis from survival median a with EB and scarring.SCCistheleading causeofdeathinthisform wounding trauma, repeated of sites at predominantly arise and and oftengetmultipleprimaries. Tumours behaveaggressively patients developcancersfromadolescenceorearlyadulthood mucocutaneous squamous cell carcinomas (SCCs). In GS-RDEB, dystrophic EB (GS-RDEB), is associated with the development of Epidermolysis bullosa (EB), notably generalised severe recessive Foundation Trust, London St John’s Institute ofDermatology, Guy’s andSt.Thomas’ NHS Jemima Mellerio THERAPEUTICS CANCER AND CANCER OP88 studies arestillongoing. the near future. Results are currently blinded/ unavailable and in participate to expected sites other with University, Stanford at healing wound as well and correction, molecular safety, for taking placewithseveralpatientsnowbeingdosedandstudied is patients RDEB to collagen VII purified of delivery travenous of proteintherapyforRDEB.Currentlyaphase1/2trialin In addition, exciting new developments are occurring in the area complementary or synergistic, however this remains to be tested. possible thattheseexvivoandingenetherapiesmaybe JEB epidermalautograftsachievedinrecentyears.Itisquite and agroupinItaly/Austriawhoarebuildingonprogressfrom equivalents, skin autologous fibroblast and epidermal corrected gene employed be will who France in one including trials, new pick upspeedinthenearfuturewithgroupseuropeentering to continue will and exciting, and paced fast been has RDEB of therapy gene with progress the total, In stage. trials clinical 3 tings. The B-VECtherapyisalsoapproaching thepivotalphase patients worldwidewhodonothaveaccesstospecializedset RDEB many reach to potential the with biopsies, for need the withoutproducts the of offshipping as shelf well the as setting, ease of application as a wound dressing gel, ultimately in a home as theexvivotherapiesdescribedabove. Advantages wouldbe therapies wouldtheoreticallynotbeexpectedtoasdurable that while the risk of insertional oncogenesis is not present, these reapplication. Disadvantagesoftheinvivoapproachwouldbe durable woundhealingwithoutsafetyissuesevenuponrepeated therapy indicates robust molecular correction, positive effects on B-VEC the of reports interim unavailable, and blinded still are data skipping exon the pediatric. While are which of 4 patients, tent HSV-1 - COL7A1 vector (B-VEC) which has been used in 10 approach involvesatopicalgelcontainingreplicationincompe Stanford, including 2 pediatric and two adult patients. The other at 3 treated, been have patients 4 approach, this In protein. VII and productionof a slightlytruncatedbystill functional collagen cleotides which act at the RNA level to induce exon 73 skipping, oligonu containing gel topical a involves first The approaches. gene therapyforRDEB.Stanfordhasparticipatedintwosuch tightly coordinated. An alternativeapproach is invivoCOL7A1 be to needs production cell and shipping of timing the and unit, including placementeitherinoperatingroomordayprocedure hospitalization requires patients to applications patient, each on detected. In addition, each approach requires a manufacturing run ex vivolimitsthesystemicriskofthisandnocancershaveyetbeen vectors that are employed, however having the gene transfer occur include atheoreticalriskofinsertionaloncogenesisduetothe and studies are now entering pivotal phase 3 trials. Drawbacks have demonstrated the longest track record of efficacy and safety wounds. The advantagesofexvivogenetherapiesarethatthey chronic and skin intact both into injected are which fibroblasts 24 EB2020 1 st WorldCongressonEpidermolysisBullosa - - - - dermal fibroblasts to a myofibroblast-like phenotype with drive a trans factors growth and cytokines pro-inflammatory RDEB, In 2018). al. et (Cho SCCs EB surrounding tissue inflamed in (Cho et al. 2018). Interestingly, APOBEC genes are upregulated of APOBEC enzymesignaturemutationsnotseeninUV SCCs levelhigh a is there tumours, GS-RDEB in contrast, In cancers. GS-RDEB in lower much is this signature, mutation UV high a carry SCCs UV-associated whereas However, 2018). al. et (SansDeSanNicolas TP53 CDKN2A, NOTCH1, HRAS, e.g. (UV)-induced SCCsinnon-EBpatientsareessentiallythesame has demonstratedthatgenesmutatedinRDEBandultraviolet identifying potential areas for targeted treatment. Genetic analysis include surgery, chemotherapy, radiotherapy and newer immun SCC EB for modalities treatment Current 2019). al et (Riihilä in SCCsshowingreducedcellviabilityandincreasedapoptosis upregulation of complement 1s and 1r, with knockdown of both as apotentialfactorinEBSCCdevelopment;RDEBSCCsshow identified been also has system immune innate The 2018). al et (Nyströmpredisposition SCC to further leading RDEB, in been which maycontributetotheincreasedmicrobialcolonisation macrophage and neutrophil mobilisation via cochlin processing, to increasedbacterialbioburdeninRDEBthroughabolitionof RDEB in SCCs. Lossofcollagen VII inthespleenandlymphnodesleads role indirect and direct a have may which flagellin al 2015). Toll-like receptor-5 (TLR-5) is a receptor for bacterial highlighted asacontributortoEBSCCdevelopment(Hosteet been also has colonisation Microbial SCCs. of EB-associated behaviour the to contribute also may so types, cancer other in 2018). It is also related to aggressiveness and metastatic potential VII null mice and RDEB patients (Esposito et al 2016; Liao et al having a role in other fibrotic diseases, and is elevated in collage severity. Interleukin 6 (IL-6), in particular, has been identified as disease with correlates GS-RDEB in Inflammation 2019). al et effect (Condorellipro-fibrotic a have and RDEB in upregulated are which miRNAs specific identified also has research Recent (Odorisio et al 2014; Anatosova et al 2019; Cianfarani et al 2019). correlated inverselywithclinicalseverityinRDEBpatients inhibitor of TGF-b, is reduced in RDEB mouse models and endogenousalso an decorin, and levels, TGF-b increases turn in which thrombospondin releases VII collagen of Loss 2017). al. provoke a stroma-led predisposition to SCC in EB (Guerra et may and stiffness matrix extracellular increases which SCCs, criptome similar to cancer-activated fibroblasts in UV-associated in the day to day management of patients with all types of EB, of types all with patients of management day to day the in Whilst itcansometimesfeellike wehavemadelittleprogress Great Ormond Street NHSFoundationTrust Anna E.Martinez STRATEGIES ADVANCES INCLINICAL MANAGEMENT OP89 SansDeSanNicolas etal.JInvestDermatol.2018;138:1423-27. Riihilä etal.BrJDermatol.2019;3 Odorisio etal.HumMolGenet.2014;23:3907-22. Nyström etal.ProcNatl Acad SciUSA.2018;115: E705-E714. Liao etal.StemCells.2018;36:1839-50. Hoste etal.NatCommun.2015;6:5932. Guerra etal.MatrixBiol.2017;63:1-10. Esposito etal.IntJMolSci.2016;17:1625. Condorelli etal.BrJDermatol.2019,28. Cianfarani etal.MatrixBiol.2019;81:3-16. Cho etal.Sci Transl Med.2018;10:eaas9668. Atanasova etal.JInvestDermatol.2019;139:1497-1505. to treattumours. clinically relevant and useful against these aggressive and difficult be to prove may complement or miRNAs IL-6, TLR5, spondin, thrombo TGF-b, enzymes, targetAPOBEC to drugs example, may providepotentialnewtargets forEBcancertherapies.For otherapy agents. Recent discoveries highlighted above, however, - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV from thestartgivinganoverall picture. disease as heterogeneous as EB, is to define success and efficacy another,in change no but aone in in improvement see may you interesting concept is also rather than listing outcome points when dies acknowledgethatandacceptthemasprimaryoutcome. An known aspatientreportedoutcomemeasuresandregulatorybo measures thatpatientsexperienceintheirdailylife. These are outcome meaningful clinically direct, to refer that endpoints challenge inrecruitingpatients. There isincreasinginterestin trials that require specific genetic mutations face anclinical even greater emerging and trials, clinical out carrying in challenge significant a present studies in participate can that patients of some competition among studies for patients. The limited number in resulted has studies of number the in increase the time, same patients typically cannot participate in more than one study at the As patients. the finding is money the finding after trial clinical meet itsprimaryoutcome. The mostimportantcomponent ofa be the fine line between a successful trial and one which fails to could andselectingtherightones greatchallenges poses endpoints in morethan1EUmemberstate.Finallyselectingclinicaltrial route wheremanufacturerscanapplysimultaneouslyforapproval popular modelfordrugapprovalintheEUisdecentralised for atrialinEBtrialsasitisotherrarediseases. The most design challenging most the of one also is this but trial, clinical placebo-controlled double-blind, a is design gold-standard the efficacy, at looking efficacy. When or safety primarily is this if the design. The design depends is on the question you want trial answered, clinical a of part second The 2010. in back studies is compared to 16 registered trials, 3 of which were commercial in EB across all ages, 38 of which are commercially funded. This major interest in EB and there are currently 90 studies worldwide funding fortheclinicaltrial.Overyearsindustryhasshown Clinical trials consist of three main parts. The first part is securing some oftheruleswhichshouldhopefullyreducecostaswell. have takenthatonboardandareworkingtowardssimplifying internationally bodies regulatory and true be can this tunately, view their pathway as a maze with countless obstacles. Unfor Interventional medicinalclinicaltrialsarecomplexandonecan Foundation Trust Dermatology Department, Great Ormond street Hospital NHS Gabriela Petrof CLINICALEXPLAINED TRIALS OP91 No abstractsupplied Debra of America, NewYork, USA Brett Kopelan BIOTECH COMMERCIAL DEVELOPMENT OP90 the adultserviceswithbetterveryearlycare. Perhaps thiswillbeobservedastheyoungercohorttransitioninto the incidencesquamouscell carcinoma inphase4 of thedisease. older children. In addition, there appears to be in no reduction detect yet in to harder much are affects their RDEB, with years 10 under children in benefit short-term some have MSC’s as such therapies anti-inflammatory intravenous Whilst reduced. has of RDEBarestillpresentbutthegradientseveritycurve have better growth and ascertainment of puberty. The 4 phases RDEB with Younganaemia. people and fractures vertebral and back ground chronic inflammation, the incidence of osteoporosis disease. Improvements in wound care have lead to areduction in of burden the in reduction overall an shows 2020 to 2000 from reviewing themorbidityandmortalityofchildrenwithRDEB - - 1 Do try and participate because everyone leads to better understan Last comment-Itiswonderfulthattreatmenttrialsarehappening. 5. Follow up - What happens now? The trial has endedandthe 4. Emotional Support- However practical you are, however much 3. Logistics-Participationinclinicaltrialsistimeconsuming. 2. Learning about the trial-You will be given detailed information a in child your enrolling before - risks VS benefits Potential 1. Parent View: SharmilaCollins also helpmeprocessafterthestudyended. and trial the throughout me helping it, for me Preparing process. would haveneededwassomeonetoguidemethroughthatwhole tions. subconsciously.happening was This personally I what So, not be the cure, that it is just a trial, I built up hopes and expecta even though I told myself, that this might not work, that this will not knowwhatIwasputtingmyselfthrough.didthat the questionsIhadandalsothosedidnotevenknowhad. psychological help. Without anyone taking my hand, answering all thing formewasgoingthroughthisclinicalstudywithoutany these thingsandIunderstoodwhyitisimportant.Butthehardest the to study sidealotoftimes–becauseIknewthatwillhavetodo travelling samples, blood or skin giving like things not The biggest challenge I faced taking part in a clinical study was Patient View: LenaRiedl Lena Riedl PATIENT AND PARENT PERSPECTIVES OP92 your childandfamilybefore signingup. ding andgetsus a littlestepfurtherbut make sureitisrightfor Salzburg, Austria, tion. Beprepared! that youare likely to see a deterioration in your child’s condi appreciate to difficult very is it time in away wear will effects the treatment.Iftherehasbeenimprovementbutyouknow Some trialsjuststopandthereisnoopportunitytocontinueon treatment or does it just stop whilst the analysis takes place? treatment has helped. Isthere an option to continue onthe and whocanguidethemthroughthisextrastress. one. Someonewhoyour child knows and is comfortable with This mightbebestfromaregularpsychologistifyourchildhas throughoutthetrialprocess. emotionalsupport toseek advisable emotional tollonbothyourselfandyourchild.Itisperhaps trial youmayendupbeingdisappointedwhichcanhaveabig you tryandminimisethehopesattachtoparticipatingina you aremakingbothforyourfamilyandthetrialsponsors. you decidetoparticipatemakesureknowthecommitment takes timeandyoumayhavetostayovernightforsome. When to followupvisitsafterthetrial. Travelling tothecentresalso There aremanyvisitsfromassessingsuitabilitytoparticipate better prepareyourselvesandyourchild. prepared toaskaboutthefrequencyoftheseinterventions These areoftentraumaticforsmallchildreninparticular. Be also oftenrequireextrabloodtestsandperhapsskinbiopsies. questions if there are elements that youdonot understand. Trials ask and carefully it read you sure make Do ‘child’s’version. regarding thetrial.Ifyourchildisoldenoughtheywillgeta understand theproceduresthatwillbeundertaken. make sureyouquestionthedoctorsincharge sothatyoufully the potentialriskscanbediscussedamongstyoubutalways these decisionswillbemadebyparents. As achildgetsolder child small a it. With worth is benefit potential the that happy therapy islikelytocarrylarger risks. Itisimportantthatyouare benefits could be against the risks of taking part. A more invasive trial youwillhavetomakeanassessmentofwhatthepotential 1 , SharmilaCollins 2 Cure EB,London 2 Oral lectureabstracts Acta DermVenereol Suppl220 25 - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta 1 together towardsthecommongoal ofimprovingpatients’ QoL. on trustandrespect,allowingthe patientsandclinicianstowork Over time, an effective therapeutic relationship can be built, based their service offers valuable, holistic support to all of their patients. should be approachable, flexible and resourceful, and ensure that sues and priorities for that particularindividual. The clinical team between the patient and clinician in order to identify the key is goodcommunication ofclinicalcareis importantaspect most and thereforeahighlyindividualisedapproachisessential. The conditions of group heterogenous extremely an is However,EB teams, social work, and most importantly, dedicated nursing teams. dental with gastroenterology,liaison testing, genetic specialists, psychology,pain podiatry,dietetics, including patients’ QoL, of multidisciplinary serviceswhichcanhelptoimprovemanyaspects specialist centresinEnglandandtheseclinicsaimtoprovide EB four are There others. many amongst relationships, family difficult and isolation, social issues, reproductive symptoms, cal time needed for dressings, side-effects of medication, psychologi account include pain, itch, mobility and other physical limitations, into taken be to Factors QoL. on effect detrimental significantly have shownthatalltypesofEpidermolysisBullosa(EB)a tion totheirgoals,expectations,standardsandconcerns.Studies of thecultureandvaluesystemsinwhichtheyliverela an individual’s perception of their position in life in the context The WorldOrganisationHealth as (QoL) Life of Quality defines Natasha Harper TOGETHER BULLOSA: PATIENT AND CLINICIAN WORKING QUALITY OF LIFEINEPIDERMOLYSIS OP95 pounds willlookafterthemselves” the pennies the of care take you “if set, data minimal a on focus undertaking aninternationalcollaborationofnationalregistries When vital. is harmonisation data data, international of sharing particularly ifapatientportalisdeployed. When itcomestothe tional average.RegistriescanbeusedforQualityofLifestudies country’s outcomesagainstanothercountryoranInterna tion betweennationalregistriesmakesitpossibletobenchmarka support Post Authorisation Safety Studies. International collabora investment andregulatorybodiessuchastheEMA requiredatato so healthbodieswanttoseeimprovedpatientoutcomesfortheir of newdrugsortreatments.Newhightechareexpensive benefits outcome and cost the support to required data the ding can support the Heath Technology Assessment process by provi multiple countries. Once new drugs have been identified registries when patients of a particular rare genotype can be identified across cohorts suitableforclinicaltrials. This canhaveextrarelevance patient of identification the in assist can Registries treatments. their health providers when motivating for improved facilities and relevant data that can support the interaction between patients and particularly forpatientswithrarediseases.Registriescanprovide access topatientdemographics governmental bodieshavelimited Registry data can play a significant role in patient advocacy. Most National &InternationalSkinRegistrySolutionsCLG Godfrey Fletcher USING REGISTRIES&BIGDATA OP94 No abstractsupplied Paracelsus MedicalUniversitySalzburg, Austria Christine Prodinger CHALLENGES OF CLINICAL TRIAL DESIGN OP93 26 mingham, Adult EpidermolysisBullosaService,UniversityHospitalsBir EB2020 1 2 Patient 1 & st WorldCongressonEpidermolysisBullosa Assya Shabir 2 ------order tooptimizepsychosocialdevelopmentinachildwithEB. support andsocialservicesshouldworktogetherwithparentsin for a child to attend school as frequent as possible. Psychosocial can helptopreventortacklethesebarriersandmakeitpossible of barriersforchildrenwithEBtoattendschool.Socialsupport lot a be can However,there world. the explore and friends meet it is also a place where children can experiment with social skills, a child with EB. It doesn’t only serve academic achievement, but Going to school is from great importance for every child, so also parents totakecareofthemselves. andencourageempower atanyway families those to support help during a certain period. Social services should focus on how anxious child. Sometimes there can be a need for respite or extra to handlebehaviourduringwoundcareorhowcopewithan how about periods difficult those during advice give can EB in be verychallenging. A healthcareprofessionalwithexperience Raising achildwithseverechronicalcondition like EBcan confronted withatypicalandcomplexbehaviouroftheirchild. lot ofpracticalissuesarenottheonlyissues. They canalsobe with agreatamountofcarefortheirchild. Wound careanda cope to have they feelings, those Beside health. psychological This canhaveanenormousimpactontheirownwellbeingand diagnose ofEBisforparentsareallyhardburdentodealwith. that social services should focus onat home andatschool.De and different contexts. sometopics address will This presentation guide the child into adulthood in different phases of development psychosocial supportcanbeimplementedfromayoungageto developmental goalunderstress. Therefor itisimportantthat complex consequences of EB can put the achievement of every different developmental stages ofpsychosocial development. The However, asforanychild,itisimportanttheycancompletethe with alotofissuesduringtheirchildhoodandadolescence. struggle may they disease, this of Because it. from suffer who enormous impactonthepsychosocialdevelopmentofchildren Epidermolysis Bullosa(EB)isamedicalconditionwithan University HospitalLeuven,Belgium Sam Geuens SOCIAL SERVICES EDUCATION AND FAMILY SUPPORT/CARE & OP97 No abstractsupplied Debra of America, NewYork, USA,DEBRA UK Brett Kopelanand FAMILYCOMMUNITY AND OP96 are recruited from the DI CPG network (N tients. The compositionoftheworking panels andsupportteams infographics wouldhavebeendeveloped withoutthedriveofpa EB or PVs, CPGs, that unlikely is it organisation, patient a for visual summariesoftheCPGs. Although anunusualundertaking live, DI’s EBWB team have been developing EB infographics; a to participatemoreactivelyintheircarenomatterwherethey mendations remain consistent in all settings and to help patients this stagethusimprovinghealthcare. To ensurethatkeyrecom tion and implementation stage, the patient versions (PVs) support the condition. The CPG development cycle requiresadissemina bullosa (EB)inordertoimprovetheclinicalcareofpeoplewith forEpidermolysis (CPG) develop clinicalpracticeguidelines DEBRA International is undertaking a long-term initiative to DEBRA InternationalCPGCoordinator Kattya Mayre-Chilton VERSIONS, AND EBINFOGRAPHICSUPDATES CLINICAL PRACTICEGUIDELINES,PATIENT OP98 Simone Bunting = 340+). This network - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV are limitations ofhigh quality evidence based literature in patients 3–5 years after publication in order to update the guidelines. There pertaining totheprovisionofOT inEBwillbeundertakenevery bFQ4c. It is anticipated that a literature search for new evidence https://rdcu.be/ link: Direct (2019)14:129. s13023-019-1059-8, https://doi.org/10.1186/ Diseases, Rare of Journal Orphanet by epidermolysis bullosa: clinical practice guidelines was published mendations tofurtherguidepractitioners.Occupationaltherapyfor by expert panel members were added to supplement the recom articles were chosen for the final recommendations. Additional files by the panel usingstandardized methodology. Postappraisal27 articles were specific to the EB population. Articles were appraised 56 these of articles, 70 identified search The format. systematic retention, and oral feeding skills. Literature was gathered using a and development motor fine (non-surgical), function hand of maximization ADL, instrumental in independence living, daily professionals. The outcomes include independence in activities of survey of persons with EB, caregivers, and experienced healthcare to prioritizetheoutcomes.Fiveoutcomesweredeterminedby topics relevant to OTs working with patients with EB in an effort on focused and created was survey scoping a 2017, In OT. for International with the goal of creating a clinical practice guideline national panelof11 memberswasco-ordinatedthroughDEBRA foundation of knowledge to guide practitioners. In 2016, an inter Intervention based onresearch has been needed to establish a trial anderrorwithcollaborationbetweencaregiverpatient. and expertise clinical care, anecdotal on based been has EB Historically occupationaltherapy(OT)practiceforpersonswith Lucile Packard Childrens HospitalPalo Alto, California,USA Jennifer Chan OCCUPATIONAL THERAPY INEB OP100 No abstractsupplied EB patient,UK Amy Price THE IMPORTANCE OF EXERCISEINEB OP99 different aspectsofEBclinical care. for infographics EB and PVs, CPGs, individual many for plans its over course considerable steps were taken to progress and strengthen and goals initial its exceeded far project The 2020. in in low resource countries, are aimed for full international launch living people support to booklets, obtained. These was feedback patient direct and piloted clinically was Infographics” EB Skin: infographic booklets are EB planned. In 2019, eight “The Health 2017, Body and Since website. International DEBRA the from downloads free for available therapy”. be “occupational will All and “psychosocial” care”, wound of “fundamentals “podiatry”, diagnosis”, “laboratory were areas clinical The 2020. in launch PVs of CPGs recently published was undertaken with the aim to childbirth and aftercare”. Since 2018, the development of eleven “pregnancy, and therapy”, hand and surgery “hand “anaemia”, “sexuality”, “physiotherapy”, of areas the in developed PVs and published be to CPGs six expect we 2020 In procedures”. clinical and “anaesthesia and “transition”, nutrition”, parenteral and “enteral care”, “palliative care”, “neonatal start: to ready are and funding awarded been have five and applications CPG seven received We access. open published were four therapy”; “occupational and “psychosocial”, “constipation”, “podiatry”, diagnosis”, “laboratory of fields clinical the in CPGs five pleted and experiences to develop the following project. In 2019 DI com people living with EB volunteer their time, knowledge, expertise and researchers experts, social and clinical EB international of - - - research areindicated. EB toprovidepsychosocialopportunityandcare.Directionsfor should workcollaborativelywiththosearoundtheindividual be well supportedandeducated about thecomplexity ofEB. They families shouldbeabletoaccessasupportivenetwork.HCP should social participationtopreventisolation.PeoplewithEBandtheir life andpsychosocialwellbeing.Interventionsshouldstimulate including psychological guidance, in order to improve quality of families living with EB need access to multidisciplinary support, and People made. be can recommendations General field. the in HCPand working caregivers and family EB, with living viduals indi for made were recommendations papers, those in evidence coping, family, wellbeing, access to HCP and pain. Based on the life, of quality exploration: and synthesis data allow to groups processes. Includedpaperswereallocatedto6different outcome The resultingpapersunderwentsystematicselectionandcritique tish IntercollegiateGuidelinesNetwork(SIGN)methodology. literature reviewwasconductedbythepanelfollowingScot and people living with EB was formed. A systematic international disciplinary panelofsocialandhealthcareprofessionals(HCP) optimise psychosocialwellbeinginEB. An internationalmulti based guidelinehasbeenmadetoproviderecommendations DEBRA International and funded by DEBRA Norway, evidence- resulting inskinfragilityandothersymptoms.Commissionedby Epidermolysis Bullosa(EB)isagroupofraregeneticdisorders UMCG Netherlands Petra deGraaf PSYCHOSOCIAL GUIDELINES OP101 experts intheroleofdifferent nutrientsinoptimisingtheirhealth. Part oftheconsultationneedsto be educationalsopatientsbecome eat. Wherever possible we need to find solutions for these barriers. as eating alone, eating different things to peers, taking too long to dental cariesorpsychologicale.g. reducedpleasurefromeating painful mouth, blistered constipation, stricture, oesophageal e.g. tient whatarethebarrierstoeatingwhichmaybephysiological To optimisenutritionalintakeweneedto identify withthepa St Thomas’ Hospital,London Lynne Hubbard NUTRITION INEPIDERMOLYSIS BULLOSA OP103 2. Intong LRA, Choi SD, Shipman A, Kho YC, Hwang SJE, Rhodes LM, Walton JR, 1. PillayE.CareofthewomanwithEBduringpregnancyandchildbirth(internet). References well ashealthcareprofessionalsinternationally. patient-centred recommendationsforwomenlivingwithEBas andhowthismaytranslateintoconcise literature review based recommendations. We discusstheresultsofasystematic work intendstoaddressagapinexpertconsensusandevidence- received littleattentioninthemedicalliteraturetodateandthis childbirth andaftercareinthecontextofEB. This domainhas We report on the development of clinical guidelines in pregnancy, St John’s InstituteofDermatology, StThomas’ Hospital, London Danielle Greenblatt PREGNANCY EB AND OP102 reveal areasneedingfurtherresearch. to serve also guidelines These services. OT requiring EB, with Int J Womens Dermatol.2017Feb 16;3(1Suppl):S1-S5. of pregnancyandchildbirthinepidermolysisbullosa Australia andNewZealand. Chapman MG, Murrell DF. Retrospective evidence on outcomes and experiences care-of-a-woman-with-eb-during-pregnancy.pdf https://www.debra.org.uk/downloads/community-support/ from available 2006 Oral lectureabstracts Acta DermVenereol Suppl220 27 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta their skinreducing synthesis from sunlight. Correction using solu patients withEBareatriskoflowvitaminDastheyoftencover it is important in muscle strength, inflammation and immunity. All of inflammation. Wider research into the role of vitamin D shows bone densityinpeoplewithEBreducingtheriskoffracturespite activity andthiscancontributetoqualityoflife. social a as eating enjoy nutrition, optimise to possible is it goals In conclusionbyworkingwithapersonwhohasEBtosetjoint mobility can be reduced due to hyperkeratosis, blistering and pain. offering weightmanagementsupport toadultswithEBSwhere reduce absorptionofironandcalcium. We alsoneedtoconsider can inhibitors pump proton gain, weight cause can Pregabalin benefits need to be considered e.g. iron the and opiates result in constipation, versus effects side and burden a become can This infections. or reflux pain, treat to medications multiple on are fully consentualevenifthisdiscussiontakestime.Manypatients placement ideallyusingalaparascopictechnique.Itneedstobe to beperformedinacentrewithexperienceofgastrostomytube have become intolerably stressed at meal times. However it needs family and child the or medication oral all refuses defaecation, tried and failed, puberty may be jeopardised, has intractable painful if apatient:hasfalteringgrowth,oralsupplementationbeen be aneffective treatment.Gastrostomyplacementcanbehelpful Ferinject (ferriccarboxymaltose)intravenouslyhas been found to be responsivetooraliron.Underthesecircumstancestheuseof in constipation and the anaemia of chronic inflammation may not can begivenorsolubleiron.Howeverironmedicationresult in EB.Ifthecauseisdietarythenadviceonsoftfoodshighiron patients withswallowingproblems. Anaemia isacommonproblem provedtobeeffective has orsprays ble vitaminD andacceptableto achieving aBMIabove18.5kg/m sing calcium, vitamin D, protein, mobility, attaining puberty and is needed. Ofequal importance is considering bone health. Optimi large wounds a diet high in energy, protein, vitamins and minerals It iswellunderstoodthatforthosewithseveretypesofEBand 28 EB2020 1 st WorldCongressonEpidermolysisBullosa 2 canleadtoimprovementsin - - 3. SedationandanaesthesiaforpatientswithEBundergoing dental 2. DentalimplantsinpatientswithrecessivedystrophicEB As EB is a rare disease, international collaboration among refe among collaboration international disease, rare a is EB As 1. OralhealthcareinEB. This sectionfollowsastandardmet of threesectionsfocusedon: topics. The originalOralHealthCPGisnowdividedintoaseries became necessarytoupdatetheguidelineconsideringemerging It updated. been have methodologies the and changed, have ties patients’published, been has evidence new 2012, in (EB) priori on OralHealthCareforindividualswithEpidermolysisBullosa Since the publication of the first ClinicalPractice Guideline (CPG) Chile, Santiago,Chile Special Care DentistryUnit,Faculty ofDentistry, Universidadde Susanne MarieKrämer ORAL HEALTH (CLINICAL GUIDELINEINEB) OP104 few months. skin condition. The newguidelineswillbepublishedinthe next rence centers is keyforimprovingthe care of patients with this Furthermore, this section considers the different stages of pa of stages different the considers section this Furthermore, after surgery based on available evidence and expert consensus. and during before, fragility skin of challenges the managing of 25volunteersfrom 11 countries. Itwillassistcliniciansin treatment. This sectionwasdevelopedbyaninternationalpanel the patient’s qualityoflife. the impactofasuccessfulimplantbasedoralrehabilitationon highlights and techniques, on guidance provides It countries. 10 from volunteers 24 of panel international an by developed on GRADEmethodologywith24PICOquestions. This was (RDEB). This sectionfollowsastandardmethodologybased with continuousfollowup. protocol preventive a of establishment the and dentist, the to from 13countries.Ithighlightstheimportanceofearlyreferral mendations developedbyaninternationalpanelof33volunteers hodology basedonasystematicreview. The consensusrecom products thatwillaidpatientscare. tient preparationanddetailsalistofnon-adhesivewoundcare - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Medicine, Faculty of Medicine, Freiburg, Germany, many Sisi Lu EPIDERMOLYSIS BULLOSA OF SQUAMOUSCELL CARCINOMASIN MOLECULAR AND MUTATIONAL SIGNATURES P2 report -pleaseseeresults. health. emotional and cares skin for neficial to ensureoptimalmanagement.IntroductionofLibrapumpbe and informationmustbesharedbetweenendocrinologyEB of betternutrition.Howevershemustbecontinuallymonitored is likelythatoriginallyherwoundhealingimprovedasaresult It ongoing. remains study case this condition, complex another Wound management in EB is challenging at best, combined with cult toattainwhetherthisisaresultoftheimpactherdiabetes. diffi – deteriorated recently have however improved, originally professional working between teams demonstrated. 5. Wound inter Effective 4. school. in excelling happier, Patient place. in for earpricks.3.Patientgained4kgin4monthsoncedieteticplan ears. Anxiety formedaroundBMs.Librapumpreducedtheneed Regular contactwithEBteam.2.Painandwoundsdevelopedon discharged homeoncestableand parentstaughtDiabeticcare. regime changed by EB CNS for slow healing wounds. 1. Patient teams ofcomplexpatient.6.Dressingmanagement/cleansing visits from CNS/joint Endo reviews. Joint managementbetween introduced (such as cheese oryoghurt) 2daily. 5.2monthly home tient unabletoeat.Insulingivenatthesetimes.Lowcarbsnacks plan –stopovernightfeed.Bolusfeedsgivenatmealtimesifpa Advised howtoremovesafelywithSMARs.4.Effective dietetic EB dressingnotusedduetotheimportanceofstayinginplace. Standard skin) unaffected (on arm right to fixed pump LIBRA originally obtained via ears as fingers/ heels severely affected. 3. tion of IV fluids. Bowels opened once electrolytes stable. 2. BMs effective weightgain.1.DKA correctedlocallywithadministra support from EB dietetics to avoid sugar hits, however to promote been adjustedundertheadviceofendocrinologyteamwith full meals.Previouslyalsorequiredanovernightfeed. This has wound healing. Previously she preferred to graze, rather than eat securing herLibrapump–duetoextensiveskinfragility/poor with monitoring blood sugar levels, administering Novo rapid and hospital andwasfoundtobeinDKA.Problemshavesincearose She presentedwithabdominalpain(commoninEB)atherlocal girl withsevereRDEB,whodeveloped Type 1diabetesin2018. are easilymissed. This casestudydemonstratesan11 yearold Irritability/Fatigue; Delayedwoundhealing. Therefore thesigns gain; weight Poor with: present already to likely are RDEB with children However, children. well in recognisable normally are report - please see results. Case report -pleaseseeresults. Materials&methods:Case Introduction andobjectives: Children NHSFoundationTrust, London,UnitedKingdom Department ofDermatology, Great Ormond Street Hospital for K.E. Plevey, G.Petrof, A.E. Martinez DIABETES EPIDERMOLYSIS BULLOSA AND TYPE 1 A RARECASEOF RECESSIVEDYSTROPHIC P1 1 Rome, Italy, Hauke Busch Yinghong He Center Freiburg, Department of Dermatology, Medical Center - University Medical 1 , MariaE.Hess 4 4 Lübeck Institute for Experimental Dermatology, Ger 1 , FrankMeiss , DavidRafei-Shamsabad 2 Institute of Medical Bioinformatics and System 2 , Antonia Reimer , Antonia Results: 1 , MelanieBoerries Symptoms of type 1 diabetes i1 , Dagmar V., Dagmar Bubnoff 1 , DanieleCastiglia Conclusions: 2 , CristinaHas 3 IDI-IRCCS, Case POSTERS 1 1 3 - - - - - , , (n team (n rof 1 future studiesandpotentialtreatmentsofthisdisease. of immunesignaturesandoncogenicalterationsthatcanguide SCC in a cohort of patients with EB and identified diverse arrays we haveimmunohistochemicallyandgeneticallycharacterized MEK-ERK pathwaysinallEBSCC.Conclusions: damage response, tyrosine kinases, PI3K-AKT-mTOR and RAF- wide spectrum of oncogenic mutations affecting cell cycle, DNA a also but KNSTRN) and NOTCH1/2 CDKN2A, (TP53, genes similar, while KS SCC was distinct. We found recurrently altered SCC. The mutational profiles of RDEB SCC and JEB SCC were tumour mutationalburdenascomparedtoRDEBSCCandJEB of headandneckSCCUV SCC.KSSCCshowedhigher tions. All mutationalsignaturesofEBSCCweresimilartothose SCC wereheterogeneouswithwidelyvaryingnumbersofaltera for EBSCCpatients. The signaturesofsomaticmutationsinEB the COX-2 anti-inflammatory drug could be potential treatments therapies of immune checkpoint inhibitors, EGFR inhibitors and combination SCC, EB in biomarkers immune of expression high the considering findings, these on Based patients. RDEB was higherintumorsamplescomparedtonon-tumor SCC comparedtoKSSCC. The molecularbiomarkerexpression RDEB in higher significantly were expressions IDO and PD-L1 least one immune checkpoint, CTLA-4, PD-1 or PD-L1. CTLA-4, showed high EGFR and COX-2 expression, and expression of at some commoncharacteristicsemerged. All EBSCCsamples Results: (KS) andonepatientwithjunctionalepidermolysisbullosa(JEB). syndrome Kindler with seven (RDEB), bullosa epidermolysis dystrophic recessive with ten EB, with patients from obtained molecularandmutationalsignaturesof48SCC analysed we of themostcommoncausesdeath.aterials&methods:Here, one and (EB), bullosa epidermolysis of complications major are Introduction andobjectives:Squamouscellcarcinomas(SCC) visits (n to theEBnurses(n The majorityofcontactsweremade via email ortelephonecall hospital. to admission required (23.5%) contacts Twenty-four advice on 102 occasions (mean 5.1 contacts per patient per year). gency hospital admissions. Results: scheduled clinicalappointmentsandproceduresincludingemer We includedallparent-initiatedcontactsoutsidetheirregularor ren were reviewed over a period of 12 months (04/2018-04/2019). our patients. identify thecausesandtoputmeasuresinplacebettersupport emergency admissionstoourpaediatricEBserviceinorder related totheirEB.Ouraimwasreviewallurgent contactsand defined system for capturing unscheduled and emergency contacts individuals withRDEBarecarefullydocumentedbutthereisno Introduction and objectives: Routine clinical appointments for C Prodinger DYSTROPHIC EPIDERMOLYSISBULLOSA (RDEB) WITH SEVEREGENERALISEDRECESSIVE AND EMERGENCY ADMISSIONS INCHILDREN REVIEW OF URGENT PATIENT CONTACTS P3 Record database and EB nurse records from 20 severe RDEB child NHS FoundationTrust, London,UnitedKingdom ment ofDermatology, Great OrmondStreet HospitalforChildren of theParacelsusMedicalUniversity, Salzburg, Austria, Department ofDermatologyand Allergology, University Hospital = 2 , AE Martinez , AE 27, 26.5%) which led to oesophageal dilatation (OD) in 90% = Although we observed significant tumour heterogeneity, = 3, 3%). The most common reason was acute dysphagia 3, 3%) and directly to the palliative/symptom care palliative/symptom the to directly and 3%) 3, 1 Materials & methods: , S Chottianchaiwat 2 = 92, 94%) followed by contacts during home 2 , L Holland The hospital Electronic Patient The hospital Electronic Patient Twenty patients soughturgent Acta DermVenereol Suppl220 2 , M Laimer Posters Taken together, 1 2 , G Pet- Depart- 29 - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta aged 11 andabove(mean5.8perpatient). patient) involved children under 2 years old, followed by children addressing identified issues included the setup of 12-weekly telep symptomatic treatmentwhilstwaitingforanOD.Furtheractions with severeRDEBtwodosesofdexamethasoneforacute OD with confirmed strictures. We have now supplied all patients were extremely reliable with 90% of patients going on to have an Reported symptoms of oesophageal strictures, such as dysphagia, increase inincidenceofsymptomssuchaspainanditchwithage. likely to reflect the newer families having less experience and the for urgent adviceinyoungerchildrenandthoseabove11 yearsis adequate provisionofstandardmedicalcare. The higherneed good levelofpatient/familyeducationabouttheconditionand number ofcontactsduringthe12-monthperioddemonstratesa Institute onPopulationMedicalGenetics(Inagemp),Brazil of Blumenau, gene splicing. Although anotablephenotypicvariabilityhas correct the alter to predicted variants pathogenic carry (74%) 20 them, Of diagnosis. correct the for essential be to proved result genetic surprising the index-cases 27 in Therefore, possible. not classification final the making indistinguishable, clinically are forms recessive and dominant whose subtype EB, Dystrophic Localized presented (13.2%) index-cases ten Finally, inferred. indicated, but the subtype (dominant or recessive) was incorrectly correctly was EB) (Dystrophic type EB main the (11.8%), nine In discordance. clinical-genetic a was there index-cases (10.5%) eight In (64.5%). index-cases 76 the from 49 in identified was result genetic definitive and hypothesis clinical priori a between to analyseandclassifythegeneticvariants.Results:Aconcordance ITGB4, COL7A1, and FERMT1). Bioinformatic tools were used KRT14, PLEC, TGM5, LAMA3, LAMB3, LAMC2, COL17A1, panel including the 11 genes implicated in most EB cases (KRT5, was performedthroughanext-generationsequencingmultigene genodermatoses, who inferred the type of EB. The genetic analysis cal examinationperformedbydermatologistswithexpertisein were included in the analysis. All patients were subjected to clini Brazilian patients.Materials&methods:A totalof76index-cases clinical hypothesisandthegeneticdiagnosisofasampleEB the analysedpatients.Ourobjectivehereistocompareprior of 94.2% in classification EB correct allowing mutation causal have developedapanelof11 genesthatwasabletodetectthe patients are difficult to access and also frequently inaccurate. We such as Brazil, exams to subclassify Epidermolysis Bullosa (EB) Introduction andobjectives:In low and middle income countries, 6 1 Luiza Monteavaro Mariath EPIDERMOLYSIS BULLOSA MORE COMMON THAN THE SUPPOSEDIN TO ATYPICALLEADING PHENOTYPES ARE CLINICAL DIAGNOSIS:SPLICING VARIANTS WHEN THE GENETICRESULT SURPRISES THE P4 reduced emergency contactsandhospitaladmissions. families to manage RDEB-related complications with the aim to to thegenerationofsymptom-orientatedmeasuresempower ‘emergency eye card’ for patients. This retrospective study has led procedure forsuspectedskininfectionandtheintroductionofan hone pain management clinics, implementation of a standardized eye problems(n infection (n ( 30 Kiszewski recida Frantz Hospital, Santa CasadeMisericórdia ofPorto Alegre Hospital, Federal University of Rio Grande do Sul, n = 24/27) ofcases. Other reasons forcontact were suspected skin EB2020 1 5,6 5 Federal University of Health Sciences of Porto Alegre, , LavíniaSchuler-Faccini = 2,3 16, 15.7%), uncontrolled pain (n pain uncontrolled 15.7%), 16, 3 DEBRA-Brazil, , MariaJuliana Rodovalho Doriqui = st 12, 11.8%). The majority of contacts (mean 7 per WorldCongressonEpidermolysisBullosa 1 , Juliana Tosetto Santin 4 Dr. Juvêncio Mattos Children’s 1,7

Conclusions: 2 Regional University = 16, 15.7%) and 15.7%) 16, 1 , Jeanine Apa- , 4 , Ana Elisa , Ana 7 National The low - - Clinic, UniversityofHealthSciences, Antalya, Turkey of inheritedblisteringdiseasescharacterizedbyincreasedmecha Introduction andobjectives:EpidermolysisBullosa(EB)isagroup Danica Xie NEGLECTED AREA OF CARE EPIDERMOLYSIS BULLOSA DISEASEGROUP: A REVIEW OF HAIRDISORDERS AND ALOPECIA IN P5 better comprehensiononthegeneticbackgroundinvolvedinEB. splicing variants and its respective effects are important fora frequent thanpresumed. more regarding investigations Additional be to appear rare, considered previously types, EB sical guide foralopeciainEB. is no universal validated alopecia scoring system and evaluation scarring alopeciabycausingloss ofnormalarchitecture. There like recessiveDEBandJEBcan resultinhairabnormalitiesand others sites, acral on trauma mechanical with blistering cause Conclusions: woolly hair)wereseeninpatientswithskinfragilitysyndromes. or hair fragile and sparse (short, patterns structure hair Specific scarring alopeciawasseeninalldystrophicEB(DEB)patients. was more common especially in patients with EB simplex (EBS), and fragilehairorwoollyhair. Although nonscarringalopecia patchy scalp alopecia and diffuse alopecia along with short, sparse manifestations ofhairdisorders. The mostcommonpatternswere and classification) were identified with demographic and clinical diagnosis on recommendations Updated bullosa: epidermolysis with all clinical subtypes of EB (as defined by Fine et al. Inherited these eligiblerecords.Results: were identified through scanning the bibliographies that had cited identified records were reviewed. Furthermore, additional records epidermolysis bullosa” were used. First abstracts, then full texts of diseases” and “skin fragility syndromes” and “lethal acantholytic skin “vesiculobullous and bullosa,” “epidermolysis disorders” hair or baldness or loss hair or “alopecia including terms search sensitivity, maximize To language. any in 2019 August to up 1950 January from databases electronic EMBASE and PubMed, Medline, in studies and reports case relevant all for searched presentations ofhairdisordersinEB.Materials&methods:We clinical and pathogenesis, epidemiology, the about information thecurrentliteratureinordertoprovide This studyaimedtoreview alopecia and hair disordersinEB to allow potentialintervention. clinical manifestationsandtreatmentorfollow-upguidelinesfor history, natural the about consensus no is there and overlooked a complication of EB. However, hair disorders have generally been in normal hair follicles. Thus, scalp alopecia and hair disorders are basement membrane zone. These adhesion proteins are also present involved inencodingadhesionproteinswithintheepidermisor nails andsystemicproblems. The mainproblemisgene mutations repeated blisters, erosions, poor healing and scarring, dystrophy of nical fragilityofskinandmucousmembranesresultingineasily 1 and inheritancepattern.Clinicalphenotypesvaryingfromclas effective tool for EB diagnosis, providing EB type determination counseling forpatients. The proposedgenepanelproved to bean and classifyEBtoprovideproperfollow-upstepsgenetic diagnose correctly to difficult is it patients, most to accessible not are microscopy electron and mapping immunofluorescence middle income countries, such as Brazil, in which exams such as that clinicalevaluationdoesnotsolveallEBcases.Inlowand than the supposed before. mechanism ofpathogenesisappearstobemorefrequentinEB this variant, of type this carrying patients in demonstrated been Australia, culty of Medicine, University of New South Wales, Sydney, NSW, Department ofDermatology, StGeorge Hospital,Kogarah, 3 Antalya Training and Research Hospital, Dermatology 1,2 , Asli Bilgic , Asli Although someformsofEBare quitemildandjust 1,2,3 Conclusions: Our study demonstrated , Nada AbuAlrub , Forty reportsdetailed64patients 2 , DédéeFMurrell 2 Fa- 1,2 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV and therecommendationscurrentlyadvisedbyauthor’s spe practice safe reflect to found was (2011) guidelines previous of recommended practice or case studies were to identified. The changes content significant no and reviewed were articles published this subjectremainsscarce;asmallnumberofpreviouslyunseen Ghani l’Université Laval, ronto, Toronto, Canada cie Germain fibrils or their absence at the dermal-epidermal junction (DEJ) junction dermal-epidermal the at absence their or fibrils anchoring defective to leads which (Col7), collagen VII type RDEB iscausedbymutationsin theCOL7A1gene–encoding cal stressintheskincausesformation ofblistersanderosions. bullosa (RDEB) is a rare genetic disease in which minor mechani Introduction andobjectives : Recessive dystrophic epidermolysis 1 Martin Barbier DYSTROPHIC EPIDERMOLYSIS BULLOSA PERMANENT TREATMENT OF RECESSIVE RETROVIRALGENE THERAPY FOR THE SELF-ASSEMBLED SKINSUBSTITUTES AND P7 (2019) willnextbereviewedin2022. patient experienceandensuresafety. The updatedguidance of theexistenceguidanceisultimatelyintendedtoimprove accessibility to updated guidelines (2019) and increased awareness an educationalresourcetoinformandguidepractice.Improved EB. Cliniciansarethetarget audienceandtheaimistoprovide experience whenbeingcaredforbyclinicianslessfamiliarwith explanation andunderstandingisintendedtoimprovepatient outlined inthenewguidance. The additionofphotographstoaid platforms. be madefreelyavailableandsignpostedtocliniciansonvarious and equipmentrecommendedwereintroduced.Guidelineswill dressings practice, in changes minor Some environment. cialist colleagues, for accuracy prior to publication. Guidelines (2019) were peer reviewed, including by anaesthetist the additionofphotographstoaidexplanationandunderstanding. including practice, current on based produced recommendations new and author the by updated were (2011) guidelines Existing extensive. A literaturesearchwascarriedoutandarticlesreviewed. fore theexperienceuponwhichrecommendationsarebasedis undergo clinical and surgical procedures on a weekly basis, there The authorworksinaspecialistenvironmentwhereEBpatients of theexistenceguidelinesorhowtoobtainthese. clinicians; thiswasperceivedtobebecausetheywerenotaware by accessed regularly not were (2011) guidelines previous the of thisguidancewasoverdue. There wasanecdotalevidencethat that all guidelines should be reviewed 3 yearly, therefore updating Materials & methods: Recommendation and best practice requires quality patient care based onbest practice and upto date evidence. easily accessibleandwidelyavailableguidancetoensurehigh practice andrecommendations. toproducemoreThe aimwas current reflect to updated and reviewed were 2011 in author the Introduction andobjectives:Guidelinespreviouslypublishedby tion Trust, London,UK Practitioner,Advanced Nurse Guy’s &StThomas’ NHSFounda- Karen Snelson PROCEDURES EB UNDERGOINGCLINICAL AND SURGICAL GUIDELINES FOR THE CAREOF ADULTS WITH P6 Centre, Québec, Alex Larose l’Université Laval/LOEX, Centre de recherche en organogénèse expérimentale de 2,3 , Véronique Moulin Conclusions: Recommendations for safe practice are 1,3 1,3 ,Sébastien Larochelle

1,3 4 , Andréanne Cartier , Andréanne Hospital forSickChildren andUniversityofTo- 3 CHU deQuébec-Université Laval Research 2 1,3 Centre de recherche sur le cancer de , Elena Pope 1,3 , Danielle Larouche 1,3 , Angela Dakiw Piaceski 4 , ManuelCaruso Results: Literature on Literature on 1,3 , Karim 2,3 , Lu- 1,3 - - - , MD MD, MSc tal, LondonUK, treatment ofRDEBskinlesions. for thepermanent methodmightbesuitable indicate thatthis was also restored compared to controls. In conclusion, our results of theskinsubstitutes. Adhesion oftheepidermistodermis were effectively transducedandobserved intheepidermallayer using aSINCOL7A1retroviralvector. Skinepithelialstemcells patient RDEB a of fibroblasts and keratinocytes in production Col7 restore to method efficient an Wedeveloped Conclusions: dermal-epidermal junction was maintained 28 days after grafting. produced from healthy donor cells. Finally, Col7 localization at the produced from RDEB cells. It was comparable to skin substitutes mis tothedermiswasalsorestoredcomparedskinsubstitutes produced Col7intheskinsubstitutes. The adhesionoftheepider structures. Moreover, 60% of keratin 19-expressing keratinocytes of Col7 at the DEJ as well as the presence of anchoring fibril-like the transducedcellpopulationsandweobservedrestoration and maintained in culture. Skin substitutes were produced from keratin 19-expressingkeratinocytesweresuccessfullytransduced of 80% to Up patient. RDEB this of fibroblasts of 70% and tes Wekeratinocy of 40% transduced particules viral that observed substitutes weregraftedontoathymicmicefor28days.Results: to thedermiswasmeasuredbyamechanicalpeelingtest.Skin mission electronicmicroscopy. The adhesionof theepidermis 99.33% of attempts. Patients experienced a in median of accomplished 2 (IQR:1-7) was dilation Successful 19.07%. endoscopy fluoroscopy 45.23%, retrograde endoscopyguided 33.04%using and antegrade episodes, of 90.74% in attempted were Dilations des overameanperiodofobservation of17(SD episo stricture esophageal 497 with patients 125 Weidentified were calculated.Results: forre-stenosis andhazardrisks statistics Descriptive age. of years 0-50 were who patients on centers EB international specialized, 7 involving study cohort multicenter of re-stenosis.Materials&methods:We conducted a retrospective, esophageal stricturesinEBpatientsandtoascertainthepredictors of presentation clinical frequency, the investigate to aimed We best type of intervention, outcomes and predictors for re-stenosis. losa (EB) requiring dilation. There is limited information on the gastrointestinal complicationsinpatientswithepidermolysisbul Introduction andobjectives: Esophageal strictures are the common 1 Elena Pope,MD,MSc COHORT STUDY EPIDERMOLYSIS BULLOSA: A MULTICENTER STENOSIS OF ESOPHAGEAL STRICTUREIN OUTCOMES AND PREDICTORS FORRE- P8 Chile Foundation, Santiago, Chile, Children’s Hospital, approach and analyzed by immunofluorescence as well as trans as well as immunofluorescence by analyzed and approach cells wereusedtoproduceskinsubstituteswiththeself-assembly quantified using keratin 19 as a stem cell marker. These corrected through flow cytometry. Transduced stem cell keratinocytes were SIN COL7A1 retroviral vector. Transduction efficacy was assessed keratinocytes lackingCol7expressionweretransducedusinga patients. developmentof a suitable permanent treatment to the skin lesions of RDEB the for strategy new a is graft, subsequent their and expression, Col7 for patient’scorrected the genetically cells and thedermis.Productionofautologousskinsubstitutesfrom ultimately resultinginalossofadhesionbetweentheepidermis Francis Pallison,MD University ofNewSouthWales Australia, University ofBogota Hospital forSick Children, University of Toronto, Section ofDermatology, DivisionofPaediatric Medicine, The 6 , DedeeMurrell, MD RDEB patient’s fibroblasts and fibroblasts patient’s Materials &methods:RDEB 1 , CarmenLiy Wong, MD 6 Guys Hospital,London,UK, 3 University ofMonterrey, Mexico, 4 1 , Anna Martinez,MD , Anne Lucky, MD 7 , MauricioTorres Pradilla,MD Acta DermVenereol Suppl220 5 Great Ormond Street Hospi - 1 , Julio Salas-Alanis, MD 2 , Irene-Lara Corrales, 7 5 St George Hospital, , Jemina Mellerio, Posters = 11.91) years. 2 Cincinnati 8

4 Debra 31 3 - - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Kuang Chen Tainan, Medicine, College of Medicine, National Cheng Kung University, approach. Long(>1cm)segmentinvolvementandmultipleloca procedure, however with higher complications in the endoscopic ofthedilation irrespective found excellentdilationoutcomes National Cheng KungUniversity, Tainan, National Cheng KungUniversity Hospital, College of Medicine, showed noticeable sustained improvement in IGA, suggesting a suggesting IGA, in improvement sustained noticeable showed areas treated placebo not but diacerein stopped, treatment When demonstrated modestimprovement inIGA andblisternumbers. areas treated diacerein period, treatment During well-tolerated. areas. diacerein treated areas but significantly by 99% in placebo treated area (LSA) at Week 12 increased slightly from Week 8 by 12% in treated areas, respectively. placebo Similarly, and the diacerein mean total for lesion 0 surface and 3 was baseline from reduction 2-point least at with 1 or 0 to equals IGAscore with subjects of 8 whereas placebo treated areas increased by 0.8; and the number IGA score for diacerein treated areas decreased by 0.1 from Week from placebo treated areas. During the follow-up period, the mean (VAS) score from 54 to 27, but the difference was not significant score from 2.4 to 1.9, and in mean Pruritus Visual Analogue Scale ted improvementinmeanInvestigator’s Global Assessment (IGA) treated areas, respectively. Diacerein treated areas also demonstra reduced by 56% and 34% from baseline in diacerein and placebo the end of treatment period (Week 8), mean blister numbers were period andtherewerenodrugrelatedadverseevents(AEs). At EBS patients.Diacereinwaswelltoleratedthroughoutthestudy consisting of five dystrophic or junctional EB (DEB/JEB) and four weeks. Patients were treated for 8 weeks and followed for additional 4 with diacerein 1% ointment and the other with placebo ointment. were selectedoneachpatient.Onelesionareawastreated severity and each) 5% – (1 (BSA) area surface body of terms in enrolled. were areas EB lesion of EB firmation comparable Two & methods:Patientswithclinicaldiagnosisandlaboratorycon important roleinpathogenesisofEBSimplex(EBS).Materials an play to thought is which production, IL-1b pro-inflammatory cerein is a novel NLRP3 inflammasome inhibitor that suppresses efficacy and safety of diacerein ointment 1% in EB patients. Dia (ClinicalTrials.gov Identifier: NCT03468322) are to evaluate the no FDA-approvedtherapies. The mainobjectivesofthisstudy are there Currently, membranes. mucous and skin on blistering of inherited skin disorders characterized by skin fragility, recurrent Introduction &objectives:Epidermolysisbullosa(EB)isagroup 1 Chu-Han Huang PILOT STUDY BULLOSA IN ACONTROLLED RANDOMIZED 1% OINTMENTDIACEREIN FOREPIDERMOLYSIS P9 tions werepredictiveofstricturereoccurrence. χ stricture: 1 vs {2 strictures of number included: re-stenosis for Predictors months. (IQR:4-12) stricture episodeswithamedianintervalbetweendilationsof7 32 stricture (χ HR Liao Mackay MemorialHospital,Hsinchu,Taiwan Ju Hsieh stricture:χ 1 vs 3 and 1.652 1.014, (95%CI: tion (iWRR), National Cheng KungUniversity, Tainan, 2/204- fluoroscopy,2/204- χ (8/86- antegrade endoscopy, 2 /149- retrograde endoscopy versus Complications weremorecommonwiththeendoscopicapproach TWi Biotechnology, Inc.,Taipei, = 1 , Chao-Kai Hsu 1.785 (95%CI: 1.194, 2.667)} and a long (>1 cm) segment cm) (>1 long a and 2.667)} 1.194, (95%CI: 1.785 Overall, diacerein ointment 1% is safe and safe is 1% ointment diacerein Overall, Conclusions: Results: EB2020 1 4 5 International CenterforWound Repair andRegenera- , Wei-Shu Lu 2

= 1

4.599, Nine patients from age 4 to 36 were enrolled, were 36 to 4 age from patients Nine 1 st , Jing-Yi Lee WorldCongressonEpidermolysisBullosa p 2 2 , 3 =

= 1 , 4 , I-Yin Lin 0.032, HR , Chao-Chung Yang 17.39, p value<0.000). p 17.39, 1 2 , Huang-Ling Hsu

= 1 = , Yiumo Michael Chan 2 4.293, Department ofDermatology, 1.347 (95%CI: 1.026, 1.769). p 2 3 , 2 4 Institute of Clinical =

, Wei-Ting Tu = 0.038, HR 0.038, 7.986, We Conclusions: We 1 , Yu-Hsiang p 5 Hsinchu = 1 = , Chih- 2 0.005, , 1.294 4 , Ya- - - - - logy, King’s CollegeLondon,Guy’s Hospital,London, of 6 children with mean onset at 18.7 months. Skin immunofluo formation at11.8 months.Severeanaemiawasnoticedin5out tissue granulation ocular and abnormalities dental months, 10.7 at stenosis laryngeal of appearance by followed months, 1.7 at overgranulation of finger and toenails occurred with a mean onset Periungual life. of months 2 first the within or birth at occurred were siblings.Skinfragilitywastheearliestpresentingsignand mean age5.4years(range2–8). All ofthemwerefemaleandtwo Results: retrievedfromthehospitalelectronicpatientrecords. meters were immunofluorescence, genetic analysis as well as laboratory para history,skin medical features, clinical data, Demographic LOC. confirmed genetically with children alive identify to database Materials &methods:We reviewedourcurrentpaediatricEB C. Prodinger (LOC) LARYNGO-ONYCHO-CUTANEOUS SYNDROME A CASESERIESOF SIXPAEDIATRIC CASES WITH P10 wound managementandpainrelief only. Oralmorphinegiven condition resultinginaKeratin5 mutation.Nocure-conservative ralised Severe(previouslyknown asDowlingMeara).Genetic Results: Katie White SIMPLEX GENERALISED SEVERE OF A CHILD WITH EPIDERMOLYSIS BULLOSA HYDROACTIVE COLLOIDGEL ON TO THE SKIN STUDY:THE APPLICATIONCASE OF A P11 of expert-led,multidisciplinarycare. notypic insights into LOCsyndrome andhighlight the importance and mortality. Our findings provide additional phenotypic and ge both inLAMA3.Earlydiagnosisisessentialtoreducemorbidity mutation (p.Leu3055fs in exon 33) and a 6-bp deletion in exon 52 in exon 39 of LAMA3 (c.151insG), we identified a further novel mutation insertional LOC-specific “typical” the Beside lenging. skin immunolabellingandmoleculardiagnosticscanbechal edges appearafterdelayedtootheruption. The interpretationof tissue appearbefore 1 yearofage.Hypoplasticteethwith sharp granulation ocular and stenosis laryngeal Thereafter, wounds. months of life, followed by overgranulation of the nails and skin appearing very early in life. Skin fragility starts within the first 2 syndrome delineatesthediseasecoursewithclassicalsymptoms Conclusions: This retrospectivestudyof6childrenwithLOC two, previously unreported mutations, were addition, identifiedIn inblood. LAMA3. the in present not was which skin, the from of-function mutation in exon 39 of LAMA3 was detected in DNA predicted aseverephenotype. An additionalheterozygousloss- which skin, and blood peripheral in both LAMB3, in mutation total absenceoflaminin-332onaskinbiopsywithbiallelic staining comparedtocontrolskinin5children.Onechildhad revealednear-normalrescence ornormalintensityinlaminin-332 Guy’s andStThomas’ NHSFoundationTrust, London, 1 its potentialindicationbeyondEBS. expanding possibly subtypes, EB different treat to intended was durable effect of diacerein. This study was the first time diacerein ren NHSFoundationTrust, London,UK ment of Ophthalmology, Great Ormond Street Hospital for Child- NHS FoundationTrust, London, ment ofDermatology, Great OrmondStreet HospitalforChildren L. Liu of theParacelsusMedicalUniversity, Salzburg, Austria, Department ofDermatologyand Allergology, University Hospital 4 , W. Moore We identified six children with a diagnosis of LOC, with 3 yearoldboy. EpidermolysisBullosaSimplexGene 1 , S.Chottianchaiwat 5 , M.Laimer 1 , G.Petrof 3 2 St. John’s Institute ofDermato- , J.E.Mellerio 2 , A.E. Martinez , A.E. 3 , J.A.McGrath 4 2 5 2 Viapath, Depart- Depart- 3 - - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV two hoursafterthechallenge.Results: mcg/dL 100 above to rise a or level iron serum of increase fold three- to two a as defined was absorption iron Successful hours. markers werecollectedbeforeand afterintervalsoftwotofour serum iron as well as hematologic, inflammatory, and nutritional gastrostomy tubeintheformof ferroussulfateliquid.Baseline were givenadoseof2mgelementaliron/kgbymouthorvia given ironcompleted12absorptionchallenges.Subjects anemia refractorytoorpooradherenceoralgastrostomy- anemia. Recessive DystrophicEpidermolysisBullosa(RDEB)whohad mine whetherironwasbeingenterallyabsorbedinpatientswith Introduction &objectives: The purposeofthisstudywastodeter Dermatology andPediatrics,Cincinnati,Ohio,USA the University of Cincinnati College ofMedicine, Departments of Epidermolysis Bullosa Center, Cincinnati Children’s Hospital,and rathe, MD,MPH,CristinaTarango, MD Bret D. Augsburger, BA, CCRP, Anne W. Lucky, MD,Kalyani Ma- EPIDERMOLYSIS BULLOSA PATIENTS WITH RECESSIVEDYSTROPHIC ABSORPTION WHENTREATING ANEMIAIN TESTING GASTROINTESTINAL IRON P12 Blisters. Reducedinflammationandimprovedpain. (good moisturebalance)anddebridementofdryskinfromhealing gel. long-term applicationisneededtoensurethistheworkof Further improvement. overall an be to there found I fluctuates Whilst therearemanyvariablesastowhytheskinofanEBpatient didn’t. Deadskindebrided wellwhichinturnreducedblisters. the startoftreatment. These would usually de-roofbutthey speed ofhealingconsideringtherewassomeverylarge blistersat experienced onapplication- minimal friction caused. Improved the Colloidgelwasquickandeasytoapply.The Hydroactive Nopain to positiveresults.Painreducedduereductionofre-blistering. due this with continue to plan but days 10 treatment: of Length ced. You can see from the images that the erythema has reduced. skin wasdebridedquickerwhichmeantre-blisteringalsoredu dry the and healed blisters days 10 of course the Over outcome: dry skin(whichcausesmoreblisters)andreducepain.Clinical debride healing, up Speed environment. healing moist optimal non-adherent foamforprotection.Provide rationaleforchoice: with cover needed if then daily, twice application gel Colloid infection andfacilitateroofofblisterre-attachment.Hydroactive prevent balance, moisture good Provide pain. his reduce and reduce erythema and inflammation, see a reduction in re-blistering ing phasetheyformthinscabs.Aimoftreatment: Quick healing, shallow andgranulating. When theintactblistersareinheal fragile withsurroundingerythemaandpainful.Openwoundsare the fulllengthofalimb.Physicalappearance:Intactblistersare location. either soft wipes or tubular retention dressings, depending on the covered with non-adherent foam dressings which are secured with and applied powder baby have blisters Intact expelled. fluid and ment: Wound care is performed twice daily- all blisters are lanced, be noattachmentoftheepidermislayer. On-goingmedicaltreat occasional traumaduetoEpidermolysisBullosacausing there to start againrepetitively. The causeisfromeverydayfrictionand on sizeanddepthhoweverwillthenre-blisterthecycle wound &cause:woundstypicallytake3-5daystohealdepending sheering andfriction.Wound location: All overbody..Duration of level duetoextremeskinfragility. Multipleopenwoundsfrom Description: Widespread blisters all over body, down to the dermis motor skillsduetodiagnosis.Notwalkingorcrawling.Wound every 4hours.Chronic Anaemia. Active childwithdelayedgross : Providing optimum healing environment healing optimum Providing benefits: Clinical Materials &methods:Ten patientswithRDEBwhohad Size ofwound: Wounds allvaryinsize-theycanexpand Nine ofthe12ironchal - - - - - sian NationalResearch ofMedicalUniversity consider replacementofenteralwithintravenousiron. to conventionalironsupplementswithabsorptiontestsand test patientswithRDEBwhoareanemicandnotrespondingwell in failuretotreatanemiaRDEBenterally. Itmaybeprudentto poor gastrointestinalironabsorptionmaybeanimportantfactor non-invasive and appear to be well-tolerated. We have shown that relatively are tests absorption iron Enteral benefits. intended the receiving be not may iron enteral prescribed patients EB Thus, due to bad taste and abdominal pain, constipation and/or nausea. unreliable be to tends iron enteral to Adherence inflammation. chronic and deficiency iron of combination a to due usually is prescribed forpatientswithRDEBwhohaveanemia. Anemia hr andCRP 5.8-13.5mg/dl).Conclusions:Oralironisroutinely ral less elevated than those in non-absorbers (ESR 34-115 mm/ dl, normal elevated ESR (29-75 mm/hr, normal 0-15) and CRP (1.2 -4.9 mg/ increased STFR (1.9-2.3 mg/l, normal 0.76-1.76). They also had levels. The threechallengeswithnormalironabsorptionallhad in patientswithelevatedsolubletransferrinreceptor(STFR) and lowhemoglobinlevels(7.3-11.2 gm/dl). Ten challengeswere albumin, serum low (CRP), Protein Reactive C and (ESR) rate normal iron absorption. All patients had elevated sedimentation atanypointdemonstrated threeofthetensubjects Only absorption. longer could. Another patienttwicedemonstratedalackofiron no later months 19 while iron, absorb to ability an demonstrated lenges showedinadequateironabsorption.Onepatientinitially (> with comorbidityFA andEBhighverylevelsoftotalIgE etiologic factorsofFA inmostcases. Within thegroupofchildren as identified were eggs and cereals, protein, milk cow’s taining Phadia AB). System, (UniCAPallergens household of mixtures to as well as IgE and specific serum IgE to the most important food allergens, underwent ofdeterminationtheconcentrationtotalserum tations ofthe FA in all the patients.Every patient in this study form ofEB. We analyzedallergic historyandclinicalmanifes 20 patients with simple form of EB and 62 patients with dystrophic open non-randomized observational prospective study, including wereenteredthis to16years EBagedfrom2months patients with to foodproteinsinchildrenwithEB.Materials&methods:82 the clinical manifestations of food allergy (FA) andIgE-response adequate diet, the study of this problem is important. To evaluate ciency in these patients and the difficulties in the formation of the these patients has not been studied, and, given the nutritional defi nutritionally compromisedgroupofpatients.Foodsensitizationin of skinandmucosa.ChildrenwithsevereEBareonethemost group ofrareinheriteddisorderscharacterizedbyseveredamage Introduction & objectives: S.G. Makarova THE RESULTS OF THE OBSERVATIONAL STUDY CHILDREN WITH EPIDERMOLYSIS BULLOSA. FOOD ALLERGY AS COMORBIDCONDITIONIN P13 of theskinandmucousbarrier. The presence oftheFA shouldbe EB andmaybecausedbyaviolation oftheprotectiveproperties Comorbidity withFA is high in patients with dystrophic formof of FA (p presence the and (%) infection skin skin(%), denuded/ulcerated positive correlationbetweensuch indexesasBodysurfaceareaof 1 T.R. Chumbadze of theMinistryHealth of theRussianFederation, of EB and in 24.2% - with dystrophic form of EB). Products con in 20.7% of children with EB (in 10% of cases with simple form FSAI ‘National Medical Research Centre of the Children’s Health’ 1,000 kUA/l) were detected most frequently.most detected were kUA/l) 1,000 Wea discovered < 0.05) and the level of total IgE (p < 0.40), but these inflammatory markers were in gene Results: 1,2 1 , E.T., Ambarchian , N.N.Murashkin FAidentified was manifestations) (clinical Epidermolysis bullosa(EB)referstoa 1 1 Acta DermVenereol Suppl220 , R.V. Epishev <0.05). Posters 1 , O.Ereshko 2 Conclusions: Pirogov Rus- 33 1 - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta tics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Pharmacological Sciences, Mount SinaiCenterforBioinforma - the ageof27.4 1 Alexandros Onoufriadis MANAGEMENT OF CHRONIC WOUNDS INRDEB REPURPOSED DRUGSFORIMPROVING IDENTIFYING POTENTIAL NEW AND P15 was 26.7 (F:M males extremities. SCCwasslightlymorefrequentinfemalesthan with SCC. The mostcommonlocalization oftumorswerelower form, HS-RDEB. Eleven patients with HS-RDEB were diagnosed severe most the had 46 patients, DEB 95 Of syndrome. Kindler had patient one and simplex, EB had 12 EB, dystrophic had 95 hology, age at the time of SCC diagnosis. age, gender, tumor localization, tumor differentiation by histopat histopathologically. In EB patients, the analyzed parameters were: confirmed was SCC of diagnosis microscopy.The electron sion transmis by confirmed were diagnoses Clinical 2019. to 1975 from Serbia, of Center Clinical Dermatovenereology, of Clinic the at followed and diagnosed EB hereditary with patients 108 ferentiated. dif well histopathologically generally are and extremities, the on predominantly preponderance, gender no with years, 40 and 35 of ages the between develops usually SCC RDEB, In areas. more frequently times in men 1.5-2.2 than in women, age, predominantly on of sun-exposed years 80 and 70 between develops SCC by the age of 40 years. In general population, SCC commonly mortality. PatientswithHS-RDEB usuallydiefrommetastatic general population, and they carry very significant morbidity and RDEB patientsgenerallybehavemoreaggressivelythanSCCsin Dystrophic EpidermolysisBullosa(HS-RDEB). Tumors inHS- wounds and scarring, particularly in Hallopeau-Siemens Recessive blistering, skin chronic of sites at arise to tend SCCs associated Kindler syndromeasarelativelyrecentlyaddedEBsubtype.EB- with cleavage, skin of levels ultrastructural on based (DEB), EB dystrophic and (JEB), EB junctional (EBS), simplex EB types: blisters, erosions and chronic wounds. There are three main sub rogeneous groupofskindisordersmanifestingwithwidespread Introduction &objectives:Epidermolysisbullosa(EB)isahete J. Lalosevic BELGRADE, 1975-2019 OF CLINICOF DERMATOVENEREOLOGY IN EPIDERMOLYSIS BULLOSA –EXPERIENCE CARCINOMA INPATIENTS WITH DYSTROPHIC INCIDENCE OF SQUAMOUSCELL P14 for thisseverecategoryofpatients. well asinthedietrecommendationsandchoiceofspecialnutrition identified actively and taken into account in the treatment and as 34 Medicine, Belgrade,Serbia 1 the prognosisinEBpatients. early diagnosisandtimelysurgical treatmentofSCCmayimprove rate, regular follow-up of every RDEB patient is imperative. The aggressive nature of RDEB-SCCs, its high incidence and mortality SCC wasdiagnosedin4patients.Conclusions:Giventhehighly differentiated moderately while patients), (7 SCC differentiated ra Proudfoot Biosciences, King’s College London, UK, Ma’ayan logy, Clinical Center of Serbia, St John’s Institute of Dermatology, School of Basic and Medical Division of Pediatric Dermatology, Clinic of Dermatovenereo- EB2020 1 2 ± , John A. McGrath 2.6 years. Seven patients died of metastatic SCC, at SCC, metastatic of died patients Seven years. 2.6 1 Materials &methods:Thedatawereobtainedfrom , M.Gajic-Veljic = 1

, Ellie Rashidghamat 6:5). Patients’ age at the time of SCC diagnosis SCC of time the at age Patients’ 6:5). ± 2.6 years. The mostcommontypewaspoorly st WorldCongressonEpidermolysisBullosa 1 , Chrysanthi Ainali , 1

1,2 , L.Medenica 2 University of Belgrade School of 1 , Jemima E. Mellerio Results: 2 1 , M.Nikolic , DenisTorre Of 108 patients, 2 Department of 1,2 2 , Lau- 1 , Avi - - - - - Salzburg, Austria logy, UniversityHospital oftheParacelsusMedicalUniversity Medical University, Salzburg, Austria, 1 with cytokine-cytokineinteractionssignallingand Toll-like re pathways, signalling in enriched were genes dysregulated that andGSVA GAGE using analysis showed Bothanalyses packages. we implemented a comprehensive functional pathway enrichment (2324) were shared between the two comparison groupings. Next, between theEBwand HC samples. Most of the DEtranscripts (DE) betweentheEBwvsEBnsamplesand2685DEtranscripts logFC and <0.01 of value p-adjusted a using analysis Bioinformatic wounded skin(EBw)versusnormal(EBn)orcontrol(HC). wounds, we compared the expression levels of the genes from the and genepathwaysthatmaybedifferentially expressedinEB BeadChip. Expression v4.0 using theIlluminawhole-genomeexpressionarrayHumanHT-12 extracted and quantified. Gene expression profiling was performed homogenised usingahand-heldPolytroninlysisbuffer andRNA (HC) matched for age, sex, ethnicity and body site. Samples controls were healthy from samples 6 and (EBn), individuals RDEB subjects (EBw), 6 samples from intact/normal skin from the same biopsies ofwholeskinfromtheedgechronicwoundsinRDEB punch 4mm collected we consent, informed and approval ethics that couldimprovesymptoms.Materials&methods:Following on usingthesedatatotryidentifyneworrepurposedtherapies signalling pathwaysthatgoawryinRDEBwoundswithafocus tissue and genes the investigates project this RDEB, with living are limited.Inkeepingwithamajorresearchpriorityofpeople management andtreatmentoptionsforchronicRDEBwounds significantly increased risk of squamous cell carcinoma. a At and present, fusion digital scars, mutilating wounds, inflamed healing wounds. Frustrated attempts at tissue repair result in poorly recessive dystrophicepidermolysisbullosa(RDEB)ischronic Introduction & objectives: One of themain disease burdens of these approachesmayresultin non-homologousendjoining template, repair homologous a of absence or presence the upon based correctionofRDEBhave been describedsofar. Dependent Introduction &objectives:SeveralapproachesforCRISPR/Cas9- Thomas Kocher PATIENT KERATINONOCYTES VIA HOMOLOGOUSRECOMBINATION INRDEB SUBSTRATE FOREFFICIENT GENEREPAIR PAIRED SPCAS9D10A RNPSPRODUCE THE P16 therapeutic relevance. potential assess to required be will validation functional Next, chronic woundsandprovidesopportunitiesfordrugrepurposing. analysis ofdifferentially expressed genesandpathwaysinRDEB EB patients.Conclusions: the signatures of DE genes between normal and wounded skin in opposed that compounds 50 identified analysis This signatures. of over 16,000 drug and small molecule induced gene expression which isawebapplicationthatprovidesinteractivevisualization L1000FWD, using performed were signatures expression gene EB wounds. Predictions for compounds that mimic or reverse the ceptor signalling pathways being highlighted as key players in Dirk Strunk burg, Germany, Immunodeficiency, Freiburg, of University – Center Medical Frei- – University of Freiburg, Freiburg, Germany, Center for Chronic tute for Transfusion Medicine and Gene Therapy, Medical Center tal oftheParacelsusMedicalUniversitySalzburg, Austria, Genodermatoses, DepartmentofDermatology, University Hospi- EB House Austria, Research Program forMolecularTherapyof > +/- 2 identified 2388 transcripts differentially expressed differentially transcripts 2388 identified 2 +/- 3 , JohannWBauer 1 3 , Toni Cathomen Cell Therapy Institute, SCI-TReCS, Paracelsus Our studyprovidesacomprehensive Results: 1,4 , UlrichKoller 2 , Simone Haas To assessgeneexpression 4 Department ofDermato- 1 2 , Anna Hoog , Anna 2 Insti- 3 - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV gene (c.425A>G/c.425A>G), results in high on-target cutting ef a homozygoussplicesitemutationinexon3oftheCOL7A1 carrying keratinocytes, RDEB into RNPs D10A SpCas9 paired Foundation Trust, London,UnitedKingdom Cardiothoracic, GreatStreet Ormond HospitalforChildren NHS 1 Lisinopril, Spironolactone, Furosemide, Digoxin and Carvedilol. beats. Herheartdiseaseprogressed despitetreatmentincluding and impairedsystolicfunction with multifocal ventricular ectopic the oldersiblinghaddeveloped leftventricular(LV) dilatation echocardiograms alongwithcardiac biomarkers.Bytheageof9 pathy. Therefore, cardiac monitoring was initiated with 6 monthly This particularframeshiftmutationisassociatedwithcardiomyo mutation whilethefatherwascarrierforframeshiftmutation. nonsense the of carrier was mother The 24. exon in R2586X, p. C>T,c.7756 mutation, frameshift a and 16 exon p.S711fsX4,in (DSP) testing revealed a nonsense mutation, c.2131-2132delAG, ofadesmosomal disorder.the possibility Desmoplakingene raising hair sparse and keratoderma fragility,palmoplantar skin tively withadiagnosisofsevereeczema.Examinationrevealed siblings werereferredtoourcenteratage2and3yearsrespec ter defibrillator (ICD) inserted while awaiting transplantation. The plantation whiletheyoungersiblinghadanimplantablecardiover deficiency. Theoldersiblingsuccessfullyunderwenthearttrans sense/frameshift mutations in the DSP gene leading to desmoplakin keratoderma andwoolyhairwithcompoundheterozygousnon Results: S. Chottianchaiwa FAILURE DEFICIENCY LEADING TO ENDSTAGE HEART TWO SIBLINGS WITH DESMOPLAKIN P17 mutations with high efficiency and lower adverse off-target effects. comprise animprovedapproachforprecisecorrectionofCOL7A1 delivery withdouble-nickingandoptimizedrepairtemplateswill therapies intoaclinicalsetting. We believethatcombiningRNP ble repairoutcomesarepivotalforadvancingexperimentalgene reduced off-target activity. Improved HR efficiencies and predicta from plasmids. This results in a larger number of edited cells and a shorterpersistenceinthenucleusthanCas9proteinsexpressed with accompanied efficiencies editing gene and targeting higher sgRNA ribonucleoproteins(RNPs)aregenerallyassociatedwith and secretionintreatedRDEBpatientcells.Conclusions:Cas9/ restoration C7 accurate to thus and mutation, the of correction HR between repairtemplateandendogenousCOL7A1led to the efficiency of >20%, analyzed viaNGS. DNA cleavage and precise templates into this approach results in increased HR and correction deletions) observed via T7 Assay. However, the addition of repair ficiency and a very heterogeneous repair outcome (insertions and staining. immunofluorescence and blotting western (NGS), sequencing generation next via electroporation and gene editing efficiencies were analyzed repair templatesweredeliveredintoRDEBkeratinocytesvia and 5´overhangs.RNPs with double-stranded repairtemplates ribonucleoproteins (RNPs)andrationallydesignedsingle- D10A SpCas9 paired using strategy, correction selection-free a to NHEJ.Materials&methods:We establishedandoptimized caveat, however, is the generally low efficiency of HR compared preferable. Ahighly thus is and mutations, of correction precise (NHEJ) orhomologousrecombination(HR).HRcanleadto Petrof the ParacelsusMedicalUniversity, Salzburg, Austria, partment ofDermatologyand Allergology, UniversityHospitalof NHS FoundationTrust, London,United Kingdom, ment ofCardiology, Great OrmondStreet HospitalforChildren Children NHS Foundation Trust, London,United Kingdom, Department ofDermatology, GreatStreet Ormond Hospitalfor 1 , A.E. Martinez , A.E. Wefragility,skin with siblings two palmoplantar report t1 , C.Prodinger 1 Results: 2 ,R. Andrews Electroporation ofour 3 , M.Fenton 4 Department of 3 Depart- 4 2 , G. De------Sajinovic Liverpool NSW 1 Ingham Institutefor Applied MedicalResearch, berger Monika Wimmer CELL CARCINOMASINRDEB MIRNA-10B MARKS AGGRESSIVE SQUAMOUS P18 were welltoleratedinourpatients. considered astreatmentoptionsdespitetheskinfragilitythese thy. ICD insertion, VAD insertion and cardiac transplant should be cardiac monitoring is vital due to a very high risk of cardiomyopa and subsequentpalmoplantarkeratoderma. The needforregular desmoplakin deficiency present early with skin fragility, wooly hair the cardiac transplant waiting list. In conclusion, individuals with on is and (ICD) defibrillator cardioverter implantable an had He dilated LV withseverelyimpairedbiventricularsystolicfunction. cardiomyopathy. shown aseverely has The latest echocardiogram years oldandhasrecentlydevelopedarrhythmogenicventricular dilatation withreducedsystolicfunctionatage8.Heisnow13 signs of graft rejection. Her brother first developed moderate LV ted oneweeklater. Shehasmadeanexcellentrecoverywithno donor heartbecameavailableandshewassuccessfullytransplan device weretoleratedwithminimalskinbreakdownatthesite. A had aventricularassistdevice(VAD) inserted.Surgery andthe rioration with significant fluid overload and end organ failure, she RDEB tissues, an increase in miR-10b expression was observed was expression miR-10b in increase an tissues, RDEB link between RDEB SCC malignancy and miR-10b expression in biopsies. Inagreementwiththe hypothesisthatthereisastrong skin archival to applied protocol ISH-fluorescent combined a of validated by specific qPCR analysis, and with an adapted version identify the miR-10b, as upregulated in SCC. These changes were to us allowed This skin. normal and patients, RDEB from cytes differentially regulated in RDEB-SCCs, compared with keratino keratinocytes. ducted to assess functional impact of miR-10b overexpression in Migration assays and 3D spheroid formationassayswerecon differential expressioninculturedcellsandFFPEtissuesections. fluorescence in situ hybridization (FISH) was applied to validate analysed in statistical softwareR. TaqMan qPCR and miRNA as wellrespectiveprimarykeratinocytecontrols. All datawere SCC andcSCC without RDEB background derived cultured cells 4.0 microarray was performed on miRNAs isolated from RDEB- dysregulated miRNAs.Materials&methods:Affymetrix miRNA RNA profile in RDEB-SCCs and assess a functional relevance of small the Investigate a rangeofothermalignancies.Objectives: changes associatedwiththeaggressivespreadoftumourcellsin ned. SmallRNAshavebeenlinkedtocellularanddevelopmental undefi relatively remain still malignancy in events cellular and molecular specific However,the aggressive. particularly present monogenic skindiseaserecessiveepidermolysisbullosa(RDEB) carcinomas (SCCs) in patients with a comorbid condition of the cell squamous that shown been has it Previously,Introduction: Piñón-Hofbauer Johannes-Kepler-University,Linz, Austria, moved totheurgent transplantwaitinglist.Duetofurtherdete heart failureandwasadmittedforfullinotropicsupport.She By age13shehadbiventricularcardiomyopathywithendstage Verena Wally hann W. Bauer tria cal Cell Therapy, ParacelsusMedical University, Salzburg, Aus- burg, Austria, University Hospital of the Paracelsus Medical University, Salz- Genodermatoses, DepartmentofDermatologyand Allergology, EB House Austria, Research Program forMolecularTherapyof 1 , ThomasLettner 3 , PaulDeSouza 1 Results: 1 2 , Dirk Strunk 217 Center forMedicalResearch, MedicalFaculty, 1 1 , ChristinaGuttmann-Gruber , RolandZauner 0, Australia, In this work, we first identified small RNAs 1 , NorbertNiklas 3 , StefanHainzl 4 , Julia Reichelt 4 Institute ofExperimental & Clini 1 , Michael Ablinger , Acta DermVenereol Suppl220 2 , JohannesProell 1 , EvaM.Murauer 1 3 , Albert S. Mellick Medical Oncology, 1 , ManuelaReisen 1 CampbelStreet, Posters 1 Josefina , 2 , Mila 1 , Jo- 35 3 ------, Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta (21%) 19 were obese overweight, and 9 were (10%) were (21%) morbidly 19 obese (total BMI, normal a were (45.5%) 41 underweight, were (5%) 2 patients: 90 in BMI on collected morbidly obese -≥40 kg/m and other areas of their body, if they wanted help in weight ma weight in help wanted body,they their if of areas other and mobility on impacted weight if asked also It time”). the of most mobility (1-10 with 10 “mobility limited, feet extremely blistered a surveythataskedthemtoratetheimpactoftheirEBSon patients attendingclinicwhowereobeseaskedtocomplete fragility andblisterformation. The variouscomplicationssuch of inheriteddiseasesthatarecharacterized byskinandmucosal Introduction &objectives:EpidermolysisBullosa(EB)isa group Nataliya Balatska BULLOSA DENSITY INCHILDREN WITH EPIDERMOLYSIS NUTRITIONAL STATUS AND BONEMINERAL P20 weight lossandimpactonmobility. management programmeforpeople with EBSandevaluateboth We weight asupportive toestablish plantobeginapilotstudy now obesity asnegativelyimpactingontheirmobilityandskinfolds. 31% compared with 26% for adults in the UK. Patients identified sions: The incidence ofobesityforpatientsinthissurveywas or ingroupEBSsessionswithadditionallocalsupport.Conclu consultations one to one as mainly advice dietary wanted fifteen inner thighs, 2 groin, 6 waist and 1 sock line as also affected. All as affected by their EBS and obesity, with 9 identifying bra line, 3 weight body impacted negatively on their mobility.their All 15 identified their feet felt 13 7.3, was mobility on EBS of impact Fifteen questionnaireswerecompleted. The meanscoreforthe required. was help what so, if and, nagement kg/m January and November 2018. BMI was recorded as normal - 18.5 and BMIofallpatientswithEBSattendingEBclinicsbetween weight height, the on collected was Materials &methods:Data and whetherabespokedietaryadviceservicewouldassistthem. to establishwhetherpatientsfeltthatobesityimpactedonmobility a) toidentifytheincidenceofobesityinpeoplewithEBSandb) index (BMI)mayfurtheraffect mobility. The aimofthestudywas may haveanimpactonbodyweightandincreasedmass mobility Reduced pain. and mobility reduced in resulting tering, simplex (EBS)areknowntohavehyperkeratosisandfoot-blis Introduction &objectives:Peoplewithepidermolysisbullosa don, SE Department of Nutrition and Dietetics, St Thomas’ Hospital,Lon- Lynne DHubbard AND IMPACT ONMOBILITY INCIDENCE OF OBESITY INPEOPLE WITH EBS P19 ability ofanchorage-independentaggregationtokeratinocytes. like cell stem cancer the confers miR-10b that showed studies tumor initiatingcells(cancerstemcells).Following3Dspheroid examined cells expressing miR-10b for properties associated with to confer amalignantphenotypetoRDEBkeratinocyteswenext miR-10b of ability the examine To KCs. RDEB in motility impaired to lead keratinocytes RDEB in miR-10b of expression RDEB, we performed functional assays. Unexpectedly, increased further investigate this link between miR-10b and malignancy in in SCCaswellanRDEB-SCClymph-nodemetastasis. To 36 Ukraine 1 sity, tyana Zamorska Bogomolets NationalMedicalUniversity, 3 Okhmatdyt National Children’s Specialized Hospital, 2 ; overweight-25.1-29.9kg/m 1 EB2020 1

7 EH 4 st 1,3 WorldCongressonEpidermolysisBullosa , InnaGedeon 2 . Between February and August 2019 3 , Lyudmyla Derevyanko 2 ; obese - 30-39.9 kg/m 2 Kyiv MedicalUniver Results: Data was

4 = Debra- 31%). 31%). 2 2 ; and , Te , - - - - - on the trabecular bone score (r score bone trabecular the on (-3.21 body total the at Z-score lower significantly had malnutrition multiple vertebral fractures. Children with chronic protein-energy with osteoporosis had %) (7.7. them of three children; of % 57 in registered was BMD Low %. 34.6 in found was malnutrition the totalbodyandlumbarspine.Results: ment (HAZ)formulawasusedforrecalculatingBMDZ-score adjust Height examined. 19.2% in diagnosed was stature Short wi”. “Discovery by measured was BMD obtained. were history nutrition and medical child index), mass body weight, (height, data «ОKHMATDYT».Anthropometric Hospital Specialized were carried out at the EB cabinet in Ukrainian National Children’s density. with Epidermolysis Bullosa (EB) and its influence on bone mineral the frequencyofchronicprotein-energy malnutritioninchildren cognized ascomplicationsofdystrophicformsEB. To study equivalents inallgroups.Conclusions: Childrenwithalltypesof a trendtowardsdecreasedvelocity comparedwithage-matched 23% had orthotic footwear, which were well tolerated. There was DDEB. of 67% and JEB of 100% EBS, of 88% these: RDEB, of 43% .Of 67% in present was score) Beighton the by defined (as Hypermobility (6%). walking) (toe equinovarus and (42%) shuffling pattern with high cadence and decreased single support altered load-bearing surface in contact with the floor (63%), short The pathomechanical altered gait patterns were characterised by: DDEB. (6%) 3 and JEB 5(10%) EBS, had 17(36%) RDEB, had of 59 referrals (22M: 26F) with an altered gait pattern. 23 (48%) and steplengthstudied.Results: analysed, was areas of decreased force transmission identifiedfloor and gait velocity the with foot the of area contact total The preferred speed allowing specific gait characteristics to be studied. this equipmentrequiresthepatienttowalkindependentlyattheir pressure sensitivewalkway)wasusedforassessmentofgait; noting analteredgaitpattern. The GaitRitesystem(electronic assessment physiotherapy one least at with 2009 since service of ourEBdatabasetoidentifychildrenreferredtertiary ren. population andthathypermobilitycanaffect thegaitinthesechild thesis wasthatgaitkineticsaredifferent fromtheage-normalised and identifypossiblecausesforitinthispatientgroup.Ourhypo pattern gait altered the define to was study this of (EB). aim The the roleofhypermobilityinchildrenwithepidermolysisbullosa no evidencesurroundingtheincidenceofalteredgaitpatternsand Introduction &objectives: Background: In the literature, there is M.Wood EPIDERMOLYSIS BULLOSA HYPERMOBILITY INCHILDREN WITH GAIT PATTERNS AND THE ROLEOF JOINT P21 treatment approach. refore itisimportantforearlydiagnosisandensuresappropriate NHS FoundationTrust, London,UK matology Consultant, Great Ormond Street Hospital forChildren 1 vs -0.95 and deformitiesmaydevelop.Lowbonemassfracturesre as malnutrition, anemia, growth retardation, esophageal stenosis, a great influence on bone mineral density in EB children. The children. EB in density mineral bone on influence great a Chronic protein-energy malnutritionisoneofthefactorsthathave (r body index and Z-score at the level L1-L4 (r mass body between correlation significant a found we Also, %. while inagroupwithoutmalnutritionitwasregisteredonly18.7 in eachchildagroupwithchronicprotein-energy malnutrition Clinical Specialist Paediatric Physiotherapist, Materials &methods:We conducted aretrospectivereview ± = 1.15 vs-1.18 1 Materials &methods:26 EB patients of age 5 to 20 years ± GPetrof 0.65, 0.86 SD, p < 2 , A.E.Martinez 0.01). Likewise, body mass index influenced index mass body Likewise, 0.01). p ± < 0.70 SD, 0.001). Furthermore, low BMD was found p = 2 < 0.48, We identified 48 children out children 48 identified We 0.001) and L1-L4 (-3.51 = p 0.61, Chronic protein-energy < 0.025). p 2 < Paediatric Der 0.01) and total Conclusions: ± 1.96 1.96 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV 1 unique combinationofclinicaland genomicfindings. rather than JEB-severe generalised. This is the first report of this of LAMA3intheskinresulting in theclinicalphenotypeofLOC tation inLAMB3andanadditional singleheterozygous mutation syndrome. tissue intheairwayandeyesismuchmorecharacteristicofLOC in patientswithJEB-severegeneralisedandextensivegranulation much lesssevereskininvolvementthanwewouldexpecttosee has she age, of years 3 currently is patient Our phenotype. LOC the with associated characteristically is and blood, the in present LAMA3 wasdetectedinDNA extractedfromskinwhichwasnot severe phenotype ofJEB. An additionalheterozygousmutationin in LAMB3, both in peripheral blood and skin, which predicted a laminin 332expressionintheskinandahomozygousmutation report a 3-year old child with clinical features of LOC with absent presented ingenomicDNA fromtheindividualandparents. We mutation, c.151insG, in the LAMA3 exon. This mutation was not there wasanadditional loss-of-function single-allele heterozygous DNA. Unexpectedly, in DNA extracted from the skin of this child patient. Bothparentscarriedthesamemutationintheirgenomic as a homozygous finding in both genomic DNA and the skin of the present was which 14, exon in c.1823insG, insertion, nucleotide 332. SangersequencingoftheLAMB3generevealedasingle IMF. The major findingwas severely reducedstaining for laminin was nomajorblisteringatthedermo-epidermaljunctiononskin Staining wasrepeatedonthreeseparateoccasions.Results: VII collagen(LH7.2clone)andtypeIV collagen(COL94clone). croscopy using antibodies against laminin-332 (GB3 clone), type mi immunofluorescence by examined was biopsy The parents. blood forDNA extractionwascollectedfromthechildandboth munofluorescence (IMF) staining and DNA extraction. In addition, & methods:A skinbiopsyfromtherightthighwastakenforim which mayprovidesomeinsightintodiseasepathology. Materials combination of clinical and genomic findings in a child with LOC caused bymutationsintheLAMA3A gene. We reportaunique delayed wound healing, laryngeal obstruction and blindness. It is to lead can which eyes, and larynx skin, the in formation tissue aberrantgranulation hallmarkis Its (JEB). Bullosa Epidermolysis EB serviceat6monthsold.LOCisararesubtypeofJunctional laryngo-onycho-cutaneous syndrome(LOC)wasreferredtoour Introduction &objectives: An infantwithtypicalfeaturesof S. Chottianchaiwat CASE REPORT LARYNGO-ONYCHO-CUTANEOUSSYNDROME: A GENOMIC FINDINGSIN A CHILD WITH A UNIQUECOMBINATION OF CLINICAL AND P22 pattern andultimatelyimprovefunctionalmobility. considered to improve foot posture, promote efficiency of the gait for orthoticsandsupportivefootwearwhentolerated;shouldbe and its effect on gait in the paediatric EB cohort. Assessment Healthcare professionalsshouldbeawareofjointhypermobility EBS, in our cohort it has also been noted across all subtypes of EB. joint hypermobility. Although thisiscommonlyassociatedwith to due pronation recognised: previously not pattern a in bearing our cohort, we also observed a high percentage of altered weight scarring whichleadstomovementrestrictionandcontractures.In and wounds open dressings, bulky pain, to due often tifactorial, EB commonlypresentwithanalteredgaitpattern. This ismul the ParacelsusMedicalUniversity, Salzburg, Austria partment ofDermatologyand Allergology, UniversityHospitalof Children NHS Foundation Trust, London,United Kingdom, Department ofDermatology, GreatStreet Ormond Hospitalfor Conclusions: We reportachildwithhomozygousmu 1 , C.Prodinger 2 ,G.Petrof 1 , A.E. Martinez , A.E. There 1 2 De- - - - - Russia, 1 1 sequenced miRNomeinapilotstudy. Materials&methods:Il derived, serum of profiling biomarker candidate a conducted we stream representing very stable biomarker molecules. Therefore reported toreleaseshortnon-codingmiRNAsintotheblood liquid biopsy alternative is ofgreatrelevance. Tumors have been sents a major burden for patients, therefore a sensitive low-invasive standard – histological screening of skin punch biopsies - repre them hard to detect by visual inspection only. The diagnostic gold rendering wounds, non-healing chronic in arise predominantly impaired inthecontextofRDEBbyfactthatprimarytumors is but significance, clinical high of is RDEB-SCCs of agnostics other thantumorresectionisavailabletoEBpatients.Earlydi age 55inRDEBpatients.Currentlynoapprovedcausaltreatment dered as the main drivers in rising the mortality rate up to 80% by developing particularly aggressive RDEB-SCC, which are consi recessive dystrophicepidermolysisbullosa(RDEB)areproneto (UV SCC)patientssuffering fromthemonogeneticskin disease Introduction &objectives:ContrarytoUV inducedskincancer R. Zauner FOR RDEB-SCCBIOMARKERIDENTIFICATION CIRCULATING CELL-FREEMIRNA SCREENING P23 diagnosing EBinvolveimmunohistochemistry ofskinsamples for available methods current the disease, the of heterogeneity autosomal recessive(R)inheritance. Duetotheclinical/genetic dominant(D)and autosomal EBhas syndrome. andKindler (DEB) dystrophic (JEB), junctional (EBS), simplex EB: of types main nents ofthecutaneousbasementmembranezone. There arefour caused bymutationsin19genesthatcodingforvariouscompo of raregeneticdisordersassociatedwithextremeskinfragility Introduction &objectives:EpidermolysisBullosa(EB)isagroup Julia Kotalevskaya BY WHOLE EXOMESEQUENCING RESULT OF SCREENING RUSSIANEBPATIENTS P24 which requires furthervalidationstudiesinlarger cohorts. size, sample low of limitation current the with samples of acell-freecirculatingmiRNA basedtumorpredictioninserum miRNA profile. algorithms reflected tumor presence and partially a tumor intrinsic A consensusserumsignaturederivedfromthreemachinelearning combining 29 up with one down-regulated and one stable miRNA. an auto-normalizationapproach58miRNA-pairswereformedby RDEB wasperformedbasedonfold-changeandsignificance.In nosis. Differential expression filtering comparing RDEB-SCC with informative profile able to cluster samples with positive SCC diag variable analysis, SVA) serum miRNAs demonstrated an inherent (PCA) ofnormalized(rlog)andbatchcompensated(surrogate evaluated. rithms weretrainedonserummiRNA-pairsandtheirperformance patients (n (Qiagen UMI)generatedfrommiRNAsisolatedRDEB lumina MiSeqmiRNA sequencingwasperformedonlibraries Pröll and Cosmetology Medical Faculty, Johannes-Kepler-University, Linz, Austria cal University Salzburg (PMU), Allergology, Salzburger Landeskliniken (SALK), Paracelsus Medi- pairs inanauto-normalizationapproach.Machinelearningalgo control (n EB House Austria, EB Research, DepartmentofDermatologyand Moscow Regional Clincal Research institue, Russian, 2 , J.W. Bauer 3 Moscow Scientific and Parctical Centre of Dermatology of Centre Parctical and Scientific Moscow 1 = , M.Wimmer Results: = 3) serumsamples.miRNAswerecombinedtoform 3) diagnosed with SCC (n Conclusions: Insummary we report the feasibility 1 , V. Wally 1,2 Unsupervised principalcomponentsanalysis , NataliaMarycheva 1 , M. Ablinger , 1 2 Center forMedical Research, Acta DermVenereol Suppl220 1 , T. Lettner = 2,3 3) and non-EB healthy andMargarita Geht 1 , S. Atzmüller , Posters 2 DEBRA 2 , J. 37 2 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta 1 Biology conditions usingdedicatedsampling swabs. We usedaspecial were sampledfromnormalskin. Samplesweretakenundersterile sional skinandnormal(uninvolved) skin. Age-matched controls perile wound, untreated an from taken were Samples sampled. were DEB confirmed with patients Nine Patients andmethods: abnormal bacterialpopulations within EB-associatedwounds. to developnoveltherapeuticapproachestargeting normaland healthy controls, using next generation sequencing, with the aim dystrophic epidermolysisbullosa (DEB)patients comparedto dermatoses. We aimed at characterizing the skin microbiome of ofmanymicrobiome hasbeenimplicatedinthepathogenesis conditions, thus hosting different bacterial populations. The skin system with multiple niches, each featuring unique physiological host, in both healthy and diseased conditions. The skin is an eco addresses the relationship between bacterial flora and their human project microbiome human The Background and objectives: Samuelov Liat PATIENTS DYSTROPHIC EPIDERMOLYSIS BULLOSA SKIN MICROBIOMECHARACTERISTICSOF P25 and geneticcounselingforapatient’s family. identification of gene mutation(s) and facilitates clinical prognosis in agene-by-geneapproach.NGSallowsfastandcost-effective than classicalgeneticapproachesusingPCRanddirectsequencing diagnostics ofEBthatprovidesmorecomprehensivediagnosis sents theimplementationofanewdiagnosticmethodforDNA in 20 of the 27 probands we tested. PKP1) COL17A1, COL7A1, LAMC2, DSP,LAMA3, EXPH5, DST, ITGA6, ITGB4, ITGA3, (PLEC, genes EB additional 12 in diagnoses primary provide to appear didn’t that significance COL7A1 genes. We alsofound29variantsofuncertainclinical LAMB3, KRT14, KRT5, in mutations significant identified we subtype of DEB, 1 case of DDEB, and 14 cases of RDEB. In total, EBS, 1 case of recessive EBS, 1 case of JEB, 2 cases of uncertain causality for our new variants as damaging. We identified 8 cases of bioinformatics tool. The results of the prediction programs showed Also thepredictionofcausalitywasperformedusinginsilico consider that 10 founded mutations are causative in our EB cases. reported. Genotype-phenotype correlation gives us opportunity to known mutations and 10 mutations didn’t to have been previously mutations were identified in all 27 probands. We found 18 earlier We have tested samples from 27 patients using WES. Significant mapped tohumanreferencegenome(GRCh37/hg19).Results: a sequencer (HiSeq 1500, Illumina). Sequencing data reads were on determined was sequence Nucleotide Roche). (Illumina, Kit mass parallelsequencingweusedKAPA LibraryPreparation for libraries genomic prepare to then USA), (Qiagen, Kit, Mini from fresh peripheral blood samples using the QIAamp DNA recessive DEB(RDEB)patients.GenomicDNA wasextracted were 10 EBS patients, 3 dominant DEB (DDEB) patients and 14 There EB. with diagnosed clinically previously families, lated Materials &methods:We included27patientsfrom26unre for reducingtheprocessingtimeandcostsofEBdiagnostics. Sequencing (NGS)ofmanygenesrepresentsa proper method are labourintensiveandexpensivediagnostics.Next-Generation followed by single candidate gene by Sanger Sequencing, which 38 Maya Medicine, Tel Aviv University Human Molecular Genetics and Biochemistry, Sackler Faculty of Weizmann InstituteofScience, Rechovot, Israel, Segal Eran of Computer Science and Applied Mathematics Division ofDermatology, Tel Aviv Medical Center, Departments 2,3 , Dassa Bareket, Dassa 3 EB2020 1 andBioinformaticsUnit,LifeSciencesCore Facilities 2,3 , Sprecher Eli 1 , BarJonathan st WorldCongressonEpidermolysisBullosa 4 , MiodovnikMor 1,5 1 , SarigOfer Conclusions: This studypre 1 , Weinberger, Adina 1 , Lotam-Pompan 2 , Molecular Cell 5 Department of 2,3 4 - - - - , , were features of adults withEBS localised andsevere.Painoc andoverweight Obesity 4.3years. earlyas as was toPK transition of age mean the yet, PK no and blisters plantar showed mainly (focal vs. diffuse) differed between EBS subtypes. While infants PK of appearance and frequency The observed. was PK 75.8%, dystrophy (n Ogna (n 1 Center –UniversityofFreiburg, Germany of Medical Biometry and Statistics,Medical Faculty and Medical plantar keratoderma (PK), palmoplantar hyperhidrosis, pain, infec of presence height, Weightand included. were available testing between February 2003 and July 2019 and with results of genetic all individualswithEBSpresentingtoanationalreferencecenter disease burden.Materials&methods:In this retrospective study, EBS. The objectivewastoidentifythemajordeterminants ofthis localised in even high is burden disease However, one. mildest the as regarded mostly is (EBS) simplex EB types, (EB) bullosa Introduction & objectives: Among the four main epidermolysis Antonia Reimer COURSE IS A MAJORDETERMINANT OF THE CLINICAL BULLOSA SIMPLEX:PLANTAR KERATODERMA NATURAL HISTORY OF EPIDERMOLYSIS P26 Clare L Rogers BULLOSA? FOR CLINICAL TRIALS INEPIDERMOLYSIS WHICH OUTCOMEMEASURES ARE THE BEST P27 therapeutic keyinbreakingtheviciouscircleofEBS. Early andthoroughpreventiontreatmentofPKcouldbe a high. are burden socioeconomic and personal both outdated: is circle. a wheelchair. We suggestthatthesefactorsarelinkedinavicious of requirement and obesity pain, infections, local with nificantly (P present was PK constantly. The needforawheelchairwasmorecommonwhen 8.2% (n Strikingly,months. summer during less even and m 600 than ter severely reducedmobilitywithblister-free walkingdistancesshor localised and severe subtypes. A third of patients (n curred in all EBS subtypes, but was most common and intense in mentation (n with severe EBS. Rare subtypes included EBS with mottled pig (48.4%) with localised, 11 (7%) with intermediate and 38 (24.2%) study,the 76 in thereof included were individuals 157 Aof total models. effect fixed and models log-linear mixed using assessed was variables of correlation statistics, descriptive using tion onworkinglifewereretrieved.Dataanalysiswasperformed tion, use of analgesics, requirement of a wheelchair and informa Cristina Has by specificpathogen-directedtherapies. DEB-associated uniqueskinmicrobiomewhichmaybetargeted skin. diversities (otherthanstaphylococci)whencomparedtocontrol skin of DEB patients featured significantly different microbiome uninvolved the Furthermore, skin. control to comparing when of DEB patients displayed increased staphylococcal content skin, comparedtotheiruninvolved,intactskin.Uninvolvedskin staphylococci speciesinDEBpatientslesionalandperilesional and advancedbioinformatics tools. Results: analyzed using next generation microbial 16SDNA sequencing DNA extractionprotocoltoisolatemicrobialDNA whichwasthen Department of Dermatology and EB Center Freiburg, These findings suggest the existence of a of existence the suggest findings These Conclusions: Conclusions: amilddiseaseThe perceptionofEBSas = = 13) of our cohort required a wheelchair occasionally or 6), EBS autosomal recessive (n 1 = = 8), EBS due to KLHL24 deficiency (n deficiency KLHL24 to due EBS 8), 1,2 3) andEBSwithcircinateerythema(n 1 , MoritzHess , Matthew Gibson

= 0.0356). The presence of PK correlated sig correlated PK of presence 0.0356). The 2 , LeenaBruckner-Tuderman 1,2 , JohannesS.Kern = 6), EBS with muscular We foundincreased 52) reported = 52) = 3,4 2 7), EBS 7), Results: Institute ) In = 2). , Linda 1 & ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV PhD University ofMelbourne,VIC, Australia Sydney,NSW, Australia, Hospital, Melbourne, VIC, Australia, bourne, Melbourne,VIC, Australia, 1 (wounds thatremainedopenfor at least 12 weeks)and 158 recur wounds were reported by 40 participants. 93 chronic open wounds 189 weeks, 72 to up for participants 25 in photographed serially were wounds 62 participants: 65 in evaluated were wounds 251 apples). A subset of patients completed both assessments. estimated wound size in comparison to known objects (e.g. grapes, and type wound self-identified participants group, survey the In reviewed to determine woundtype (chronic versus recurrent). traced andwoundareawasmeasured.Medicalrecordswere size,pain, and itch in a wound survey. Woundstype, in the wound photograph cohort were their on reported group another and assessments photographic wound serial had group one enrolled: Materials &methods:Two groupsofRDEBparticipantswere wounds. recurrent and wounds open chronic wounds: RDEB of types distinct two characterize and define to aimed study This losa (RDEB)iscrucialasacomparisonforfutureclinicaltrials. wounds in patients with recessive dystrophic epidermolysis bul Introduction &objectives:Characterizingthenaturalhistoryof Claudia EvaTeng, BA HISTORY STUDY EPIDERMOLYSIS BULLOSA: A NATURAL WOUND TYPES INRECESSIVEDYSTROPHIC CLASSIFICATION OF TWO DISTINCT P28 better discriminatebetweenEBtypesanddiseaseseverities. tools demonstrateexcellentreliability. The EBDASIappearsto discriminate between EBS and DDEB. Conclusions: Both scoring and RDEB and DDED and RDEB. In addition, the EBDASI could other. Both tools could discriminate between EBS and JEB, EBS The twotoolsdemonstratedstrongconvergent validitywitheach- 0.852. The ICC for intra-rater reliability was 0.99 for both scores. reliability were: EBDASI 0.942 and iscorEB-clinician (iscorEB-c) Results: of life was assessed using the iscorEB-p and QOLEB measures. in EBusingtheEBDASIandiscorEB-cscoringtools.Quality Each patientwasevaluatedby6dermatologistswithexpertise observational cohortstudywasconductedin15patientswithEB. clinical trialsinEpidermolysisBullosa.Materials&methods:An in use for best is which determine to tools, scoring iscorEB and convergent validityanddiscriminateoftheEBDASI reliability, the compare To compared. directly been never have but score, (BEBS) Severity Bullosa Epidermolysis Birmingham (iscorEB) were independently developed and validated against the Scoring Clinical Outcomes ofResearch forEpidermolysis Bullosa Disease Activity andScarringIndex(EBDASI)Instrumentfor and monitortheseverityofdisease. The EpidermolysisBullosa bility ofa valid and reliable scoring tool that can accurately assess trials in Epidermolysis Bullosa (EB)is dependent uponthe availa Introduction &objectives: Martin Jean Tang, [email protected] 1 MSc Royal Melbourne Hospital,Melbourne,VIC, Australia, Australia, ment ofDermatology, Sydney Children’s Hospital,Sydney, NSW, Dedee FMurrell NSW, Australia, Stanford, CA, Faculty of Medicine, University ofNewSouthWales, Sydney, Dept. ofDermatology, Stanford University School ofMedicine, 1 1 , Shufeng Li, M.Peter Marinkovich, MD 5 , SusanRobertson The intraclass correlation coefficients (ICC) for inter-rater 6 Department ofDermatology, TheRoyal Children’s 2 Invitae, San Francisco, CA Corresponding author: 2 1,2 Department ofDermatology, St George Hospital, 1 , DanielC.Solis,MD 3 Faculty ofMedicine,UniversityMel- 6 , BenjaminSDaniel Background: The successofclinical 4 Department ofDermatology, 7 Department ofPaediatrics, 1,3 1 , Jean Y. Tang, MD, , MelissaBarriga, 1,2 , JohnC.Su 5 Results: Results: Depart- 6,7 - - - , associated with larger with associated (p wounds significantly was severity Worsening21/83). disease (25%, skin reported as mild (26%, 22/83), moderate (48%, 40/83), or severe separate studies. This study supports the existence of these two rent wounds were reported more frequently, similar recur to findings in however wounds, open chronic in more seen were areas larger woundsizeandworseQOL inRDEB. These larger wound sions: This studyshows clinicallyimportantcorrelationsbetween 20.0 was participants) 39 by (completed self-reported skindiseaseseverity. The averageQOLEBscore osteoporosis (p history ofanemia(p based ondisease severity. Extracutaneous manifestations including cipants reported itch; there were not significant differences in itch open wounds were 40 cm healed in 12 weeks. 52% of recurrent wounds and 30% of chronic as “areas that have not healed for weeks/months”), none of which weeks. 289 were chronic open wounds (classified by participants 12 within healed which of all heal”), to difficult are that “areas wounds. 937 were recurrent wounds (classified by participants as LEB) instrument.Results: using the validated Quality ofLife in Epidermolysis Bullosa (QO extra-cutaneous symptoms, and medications. QOL was measured itch, pain, characteristics, severity,wound disease skin included rough theglobal EBCare Registry. Patient self-reported outcomes Materials &methods:RDEBpatientsweresurveyedonlineth medication burdenandqualityoflife(QOL)inRDEBpatients. comorbidities, characteristics, wound to relates severity disease (RDEB). The objectivewastocharacterizehowself-reportedskin exists inpatientswithrecessivedystrophicepidermolysisbullosa Introduction &objectives: A spectrumofskindiseaseseverity E.S. Gorell SECTIONAL SURVEY EPIDERMOLYSIS BULLOSA: A GLOBAL CROSS- OF LIFEINRECESSIVEDYSTROPHIC CLINICAL MANIFESTATIONS, AND QUALITY RELATIONSHIPS BETWEEN WOUND SIZE, P29 wound surface area (Kappa (Kappa wounds survey. These participants were able to correctly classify their 22 participants with wound photographs also completed the wound types (e.g.generalized severe) and locationon the posteriortrunk. cm wounds, rent 118.4group: cm (photographed baseline were evaluated. Chronic open wounds were significantly larger at rent wounds (wounds that healed within 12 weeks but re-blistered) these twowoundtypes. outcomes. However, larger studies are needed reported to further examine patient and course clinical differing their given trials, important to differentiate when selecting target wounds in clinical open woundsandrecurrentwounds. These twowoundtypesare This natural history study defines two RDEB wound types: chronic 1 South Wales D. Murrell was associatedwithworsequality oflifescores(p p scale, Man Itch 1.5, versus (2.4 pruritic more be to tended and wounds were significantly more painful (5.0 versus 2.4, changes (p skin disease were more likely to use analgesics during dressing routine useofopiates(p carcinoma (p Stanford School of Medicine, = 2 0.07). Larger wounds were associated with more severe sub severe more with associated were wounds Larger 0.07). versus44.7cm 3 1 = , M.P. Marinkovich , V. Eng 0.03), including opiates (p opiates including 0.03), p = = < 0.04), routine use of gabapentin (p gabapentin of use routine 0.04), = 0.03) were significantly associated with increased 0.01; survey group: chronic open wounds 66.3 wounds open chronic group: survey 0.01; 0.5, 95% CI 95% 0.5, 1 , D.Solis 2 < recurrent wounds, recurrent 0.01), gastrostomy tube use (p 2 = . Overallskindiseaseseveritywasself- = 85 RDEB patients reported on 1,226 on reported patients RDEB 85 0.02). Participants with more severe more with Participants 0.02). 1 0.6, 95% CI , S.Choi 1 = , J.Y. Tang 2 deSouzaTech, 0.3–0.8) and accurately estimate accurately and 0.3–0.8) < 0.01), history of squamous cell Acta DermVenereol Suppl220 1 , J.Nazaroff = = 1 2 p ± versus 26.0 cm 26.0 versus 0.02). 85% of all parti all of 85% 0.02). 0.4–0.8). < 9. Larger woundsize 0.01). Chronic open Chronic 0.01). 3 University ofNew = Posters 1 , M.deSouza 0.02). Conclusions: = = 0.02), and 0.02), 0.02), and p Conclu 2 = recur 0.02) 39 2 ------,

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Dearmatologico deJalisco,Guadalajara,Mexico Thomas’ NHSFoundation Trust, 1 is well tolerated, requirement for analgesia has significantly redu no cemiplimabrelatedadverse events haveoccurred. Treatment three weeksandhasnowhadeight dosesofcemiplimab. To date She subsequentlywentontohave intravenouscemiplimabevery to ulcerate. She had debulking surgery and electrochemotherapy. Over the next few weeks the SCC metastasis enlarged and began might benefit from electrochemotherapy and cemiplimab therapy. didate for curative surgery or radiotherapy, but it was felt that she tidisciplinary teammeeting;shewasnotfelttobeasuitablecan pectoralis muscle. The casewasdiscussedattheskincancermul right the abutting wall, chest upper right the on mass cm 4 x 2.9 subcutaneous SCCdeposit. An urgent MRIdemonstrateda4.3x ultrasound-guided fine needle aspirate confirmed the mass to be a was a 3cm fluctuant mass on the right upper chest wall. An urgent of theneckoneandthreeyearspreviously. Onexaminationthere had squamouscellcarcinomas(SCCs)excisedfromtherightside enlarging mass on the right upper chestwall.Shehadpreviously epidermolysis bullosa(RDEB)gavea2weekhistoryofrapidly Results: G.M. O’Sullivan BULLOSA CELL CARCINOMA INEPIDERMOLYSIS CEMIPLIMAB FORMETASTATIC SQUAMOUS P31 a fibroticandtumorpromotingECM. is absent, will result in abnormal TSP-1 secretion contributing to C7 when which, of disruption the and C7 by directed is ECM to is disrupted by dysfunctional C7. which Golgi, to ER from transport protein bulky facilitating tein TSP-1 secretion is dependent on TANGO1, a transmembrane pro in both normal human fibroblasts and RDEB fibroblasts we investigatedwhether TANGO1 participatesin TSP-1 secretion and expression, and localization TSP-1 measure to blotting tern & methods: driven TGFβ signaling leading to skin fibrosis in RDEB. aims toinvestigate the mechanismsofthrombospondin-1(TSP-1) age 50, which makes RDEB a life-threatening disease. This work squamous cell carcinoma (SCC) with more than 80% mortality by RDEB patients with chronic fibrosis carry a high risk of metastatic adhesion leading to excessive scarring and fibrosis. Furthermore, C7 inRDEBpatientsresultsdiminisheddermal-epidermal of anchoring fibrils that attaches dermis and epidermis. Defective a large extracellularmatrix(ECM)proteinandthemaincomponent tions in the COL7A1 gene, encoding type VII collagen (C7). C7 is Bullosa (RDEB)isasevereskinfragilitydisordercausedbymuta Introduction &objectives:RecessiveDystrophicEpidermolysis Qingqing Cao COLLAGEN INDERMAL FIBROBLASTS TSP1 SECRETIONISDEPENDENT ON TYPE VII P30 dressing changesinpatientswithmoresevereskindisease. study alsorevealedincreasedopiateusageroutinelyandduring carcinoma, anemia, osteoporosis, and gastrostomy tube use. This key clinicalmanifestationsincludinghistoryofsquamouscell Larger woundscorrelatedwithself-reporteddiseaseseverityand wound typesandshowsthatpatientsunderstandtheirexistence. 40 1 C. Bernardis and StThomas’ NHSFoundationTrust Foundation Trust. Jefferson University, Philadelphia, Pennsylvania, USA, St John’s InstituteofDermatology, Guy’s andStThomas’ NHS Department of Dermatology and Cutaneous Biology, Thomas EB2020 1 A twenty-eight yearoldfemale with recessive dystrophic We utilized proximity ligationassay (PLA) and wes 2 , S.Papa 1 , JulioC.Salas-Alanis 1 , J.Clapham st 2 WorldCongressonEpidermolysisBullosa Department ofPlastic Surgery, Guy’s andSt 3 , J.E.Mellerio 1 , C.Mackenzie 3 Department ofOncology, Guy’s TSP-1 secretion Conclusions: TSP-1 2 1 , Andrew P. South 1 , D.T. Greenblatt 1 Materials Materials 2 Instituto Results: 1 ------, 1 2. Mir, L., Gehl, J., Sersa, G., Collins, C., Garbay, J., Billard, V., Geertsen, P., Rudolf, amputation stumpandoptedforECT after multidisciplinarydis lymph nodedissection.Hedevelopedafurtherrecurrenceonthe metastases. Hehadaleftbelowelbowamputationandaxillary He developed a further recurrence with in transit and axillary excised SCC. This was excised and SCC confirmed on histology. male presented withanoduleonthelefthandatsiteofpreviously old year 24 a 2, Patient later. months 3 away passed and but developed metastatic deposits in the left inguinal lymph nodes the tumour. Shesubsequentlyrequiredanabovekneeamputation following ECT, but there was no significant change in the size of and 303 sequences with a linear electrode. She had short term pain to impedetumourgrowth.Shereceivedbleomycinsystemically excised SCC.ShehadECT tohelpwithmanagement ofpainand with anulceratedareaovertheleftkneeatasiteofpreviously presented who female old year 23 a was 1 Patient [1]. tolerated it waseffective forpalliativetreatment andwasgenerallywell in themanagementofavarietycutaneousmetastasesfound of chemotherapytotumours. A recentsystematicreviewofECT bullosa (RDEB).ECT involveselectroporation andthedelivery nomas (SCCs)associatedwithrecessivedystrophicepidermolysis (ECT) in 3 patients with advanced cutaneous squamous cell carci Results: G.M. O’Sullivan EPIDERMOLYSIS BULLOSA SQUAMOUS CELL CARCINOMA IN ELECTROCHEMOTHERAPY FORMETASTATIC P32 adverse events. progressing disease, with clear symptomatic improvement and no SCC, however. To date our patient has had stabilisation of rapidly no publishedreportsoftheusecemiplimabinEB-associated metastatic cutaneous SCC had an objective response [2]. There are registration phase II trial, 47% (95% CI, 34 to 61) of patients with ment of locally advanced or metastatic cutaneous SCC [1]. In the death-1 (PD-1). It is the first CPI to receive a license for the treat (CPI) thatbindstheinhibitorycheckpointreceptorprogrammed miplimab isamonoclonalantibodyimmunecheckpointinhibitor achieved withclinicalevidenceofreductionintumourbulk.Ce ced andsleephasimproved.Radiologicstablediseasebeen 1. Key references: more fullyassessitspotentialrole inthesetumours. SCC althoughfurtherexperience ofthismodalityisrequiredto for debulking and palliation in locally advanced RDEB-associated with advanced SCC [3]. Our experience suggests it may be useful there isonlyonepublishedreportdescribingECT in3EBpatients to the 2006 standard operating procedure [2]. To our knowledge, disease stabilisation.ECT treatmentswereperformedaccording tumour growthslowed.Shehasnowcommencedcemiplimabwith near electrode. ECT was well tolerated, pain control improved and bleomycin systemicallyand61sequencestothewoundwithali aspirate confirmed SCC. She had debulking surgery followed by She had previous SCCs excised from the right neck. A fine needle presented witharapidlyenlarging noduleontherightchestwall. and he passed away 2 months later. Patient 3, a 28 year old female control and sleep improved, however his local disease progressed and intravenousantibiotics.Followingthisacuteepisodehispain linear electrode. After ECT he became septic, requiring admission cussion. He had bleomycin systemically and 500 sequences with a C. Bernardis Thomas’ NHSFoundationTrust Foundation Trust, St John’s Institute ofDermatology, Guy’s andStThomas’ NHS Morley Morley J, Grocott P, Purssell E, Murrells T. Electrochemotherapy for the palliative Eur JSurg Oncol.2019doi:10.1016/j.ejso.2019.07.003. [Epubaheadofprint]. meta-analysis. and review systematic Ametastases: cutaneous of management We describeourexperienceofelectrochemotherapy 2 , A.D. MacKenzieRoss 1 , J.Clapham 2 Department ofPlastic Surgery, Guy’s andSt 1 , C.Mackenzie 2 , J.E.Mellerio 1 , D.T. Greenblatt 1 1 - - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV 3. Diociaiuti A, Rotunno R, El Hachem M, Latorre S, Cozza R, Curatolo P. Electro Tockner tion, Hospital Pharmacy, Salzburg, Austria, 1 Christina Guttmann-Gruber EPIDERMOLYSIS BULLOSA AND PAIN INPATIENTS WITH DYSTROPHIC OINTMENT ON WOUND HEALING,PRURITUS THE IMPACT OF LOW-DOSE CALCIPOTRIOL P34 such visitstoourcolleagues. all patientswherevertheylive. We wholeheartedlyrecommend renewed ourdetermination to provide the best possiblecarefor strated thedeepcommitmentfeltbythoseworkingwithEBand further exchangesandinformation-sharing. This eventdemon they didn’t wantthedaytoend. The eventhasbeenfollowedby thrilled to meet other affected families and expressed the view that rewarding on both professional and personal levels. Patients were and enriching informative, experience the found countries both was overwhelminglypositive. All thehealthprofessionalsfrom and one-to-one discussionswith the professionals. The feedback Patients travelledmanymilestobethereandenjoyedpresentations held an EB Family support meeting - the first to be held in India. Debra travelgrantsfornursesandtherapists.Onthethirddaywe EB Without Borders. The visitorswereself-fundedwithlimited from thetwocountries. The meetingwasfacilitated by Debra’s management given jointly bythe relevant healthcare professionals of presentationsonvariousaspectsEBclinicalfeaturesand from othercenterswereabletoattend. The programconsisted conference was widely advertised in India, and EB professionals team, sharing thestagewithcolleaguesfromacrosscontinent local The the with event educational day 2 a organizing and India, in centre a visiting Hospital our from team professional ambitious project was developed, involving the whole EB andmulti- unique a knowledge, sharing countries our between visits in resource-limited settings. After several years ofindividual to lookoutwardsandestablishlinkswithmedicalprofessionals particular hasarichdiversityofcultures. This hasencouragedus UK is a melting pot ofdifferent nationalities andourcity in resources andpatientsstrugglingtofendforthemselves. The minimal with working professionals medical with unaffiliated, remain countries many International, Debra of reach extensive and facilitiesarespreadunevenlyaroundtheglobe.Despite Results: Bangalore *Manipal Hospitals, Bangalore &Centre for HumanGenetics, Birmingham Women’s andChildren’s NHSFoundationTrust and James D,Hiremagalore R*,George S*,MossC,OgboliM INTERNATIONAL COLLABORATION BORDERS: A SUCCESSFUL EXAMPLEOF EPIDERMOLYSIS BULLOSA (EB) WITHOUT P33 Wolfgang Hitzl er burg, Austria, University Hospital of the Paracelsus Medical University, Salz- Genodermatoses, Departmentof Dermatologyand Allergology, fer EB House Austria, Research Program forMolecularTherapy of 8 three cases.JEur Acad Dermatol Venereol 2016;30(7):1195-1196. of report bullosa: epidermolysis dystrophic recessive with patients in carcinoma cell squamous of management the for treatment new potential chemotherapy,a by meansofinvasiveornon-invasiveelectrodes.EJCSuppl,4(11), pp.14-25. either systemicallyorlocallyandelectricpulsesdeliveredbytheCliniporatorTM administered cisplatin or bleomycin of use the for Instructions chemotherapy: electro the of procedures operating Standard Marty,M. and G. O’Sullivan, Z., 2 , RolandLang , JohnE.Common 1 , Victoria Reichl All ofusworkingwithEBareveryconsciousthatcare 2 6 Landesapotheke Salzburg, DepartmentofProduc- , FlorianLagler 8 * andMartinLaimer 3,4 , Anja Diem , Anja 1 , Peter Hofbauer 1 , Josefina Piñón Hofbauer Piñón Josefina , 7 , JuliaReichelt 5 , KatharinaUde-Schoder 8 * 2 , MartinWolkersdor 3 Institute of Medical 1 , JohannW. Bau- 1 , Birgit 5 - - - - , Allergology, ParacelsusMedical University, Salzburg, Austria, House Austria, Outpatient Unit, Department of Dermatology and wounds were photographed and swabbed for microbiome profi microbiome for swabbed and photographed were wounds treatment arm. Patients were assessed at days 0, 14 and 28, when other the to crossed-over patients phase, washout two-month a burg, Austria, Department ofPediatrics,Paracelsus Medical University, Salz- burg, Austria;*equally contributingauthors versity Hospital Salzburg, Paracelsus Medical University, Salz- designated wounds (≥ per day(containingeitherverumorplacebo)topicallyontotwo randomized intotwotreatmentarmsandapplied1gofointment on bacterial wound colonization, pruritus and pain. Patients were secondary objectives,weevaluatedsafetyandimpactoftherapy wound healing in DEB patients (EudraCt.: 2016-001967-35). As promoting in nM) 121 ≈ µg/g, (0.05 ointment calcipotriol dose cross-over phase II clinical trial to evaluate the efficacy of a low- double-blind, randomized, placebo-controlled, a initiated We cohort. patient this to benefit clinical a at sitesofinjuryandchronicnon-healingwoundscouldimpart prevalent in DEB, we hypothesized that topical VD3 application highly be to deficiency VD3 revealing evidence as well as data neoplastic effects againsttumorcells.Basedonthisfavorable anti- significant exhibited calcipotriol of concentration same the models of dystrophic epidermolysis bullosa (DEB). Importantly, microbial defenseandacceleratedwoundclosurein2Dcell culture nM ofthe VD3 analoguecalcipotrioldemonstratedaugmented previous own Consistently, defense. infection byenhancing pathways oftissue repair and antimicrobial ability ofkeratinocytestorecognizeandrespondinjury the facilitating healing, wound proper and homeostasis skin for Introduction &objectives: Vitamin factor D3(VD3)isanessential 6 8 patients withepidermolysisbullosa (EB)andprovideinnovative technology industriesstrivetoimprove healthandwell-beingof Introduction & objectives: Whilst pharmaceutical and medical Ulana Pawlak OF THIRTY YEARS OF CLINICAL EXPERIENCE EPIDERMOLYSIS BULLOSA:EVIDENCEREVIEW DEVICES IN THE MANAGEMENT OF SILICONE-BASED DRESSINGS AND FIXATION P36 accelerate woundhealingandreducetheburdenofitchinDEB. this studyindicatethattopicallow-dosecalcipotriolointmentmay is stillunderinvestigation.Conclusions:Preliminarydatafrom the trial. The effect ofeachtreatmentarmonwoundmicrobiota Importantly, no adverse effects were 28. observed at any time day during by pain reduced significantly placebo and verum Both arm. placebo the in reported was change no whereas treatment, of course the over scores itch in reduction steady and significant a in resulted Notably,calcipotriol arms. of treatment application closure equalizedwithnodifferences longerobservedbetween 65.6% in the placebo arm at day 14. At day 28, effects on wound to compared 88.4% of size wound in reduction mean significant a in resulting healing, wound accelerated treatment Calcipotriol both interventionphasesandwereincludedforanalysis.Results: a visualanalogscale.Sixoutofnineenrolledpatientscompleted ling. In addition, pruritus and pain scores were determined using 1 Economic Affairs, Mölnlycke® HealthCare, Gothenburg, Sweden Biology, A*STAR, pore, Singapore, Salzburg, Austria, Health Care, Gothenburg, Sweden, Research Office Biostatistics, Paracelsus Medical University, Medical Paracelsus Biostatistics, Office Research A BiomedicalGrove,#0 Immunos MD, GlobalMedical Affairs and Safety Manager, Mölnlycke® 1 8 andMarkF. Rosenberg Department ofDermatologyand Allergology, Uni- 4 Skin Research Institute of Singapore, A*STAR, 7 8 Institute for InbornErrors ofMetabolismand A Biomedical Grove,#0 Immunos 6 cm 2 each)overaperiodof4weeks. After 6 -0 2 Acta DermVenereol Suppl220 Medical Writer, Medicaland 6 , Singapore, Singapore, studies using 100 using studies in vitro 2 Materials &methods: Posters 6 -0 8 , Singa- 5 EB 41 - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta don, UnitedKingdom, Specialist at Guy’s andStThomas’ NHSFoundationTrust, Lon- 1 lak completed the survey. Six (32%) patients were 50 years old. Six old. years 50 survey.were the patients completed (32%) Six the products’ performanceand safety.of Results: perception and patterns, usage product diagnosis, EB data, asked tocompleteaseriesof22 questions to capture demographic dressings and fixation devices. of EBwasconductedtocollecttheir experiencesofsilicone-based with variousforms cross-sectional observationalstudyofpatients the selectionofdressingsastheyareexpertregardingtheirskin. A with epidermolysisbullosa(EB)whoshouldalwaysbeinvolvedin mes. This isparticularlyrelevanttothemanagementofpatients patients canhelpshapebestpracticeandoptimiseclinicaloutco Introduction of intotheexperiences insight Gaining &objectives: 4 Kristina Blom DEVICES SILICONE-BASED DRESSINGS AND FIXATION TO UNDERSTAND USAGEPATTERNS OF OF PATIENTS WITH EPIDERMOLYSIS BULLOSA A CROSS-SECTIONAL OBSERVATIONAL STUDY P37 EB andrelatedconditions. alleviated painandimprovedclinicaloutcomesinpatientswith the silicone-based dressings and fixation devices performed well, were dozensofpublishedcasestudieswhichdemonstratedthat changes andnoallergic reactions occurred.Conclusions:There rity ofpatients.Minimalpainwasexperiencedduringdressing foam dressing.Goodwoundhealingwasreportedinthemajo with acquired bullous conditions) treated with a soft silicone 91 yearswithbullousskindiseases(13EBand9patients Schumann et al 2005 reported on 22 patients aged between 1 and intravenous cannulaewithoutblisteringaroundtheinsertionsite. secure to used be could layer contact silicone soft the bullae, of restored previous hand function. Apart from the management complete epithelializationwasachievedwithin4weekswitha EB severe with boy old five-year a in instance, For children. in pain andanxietyduringdressingchangesinseveralcasestudies alleviate significantly to reported was layer contact silicone soft as acriticalfeaturedeterminingthechoiceofdressings. The recognized digital webbing.Non-adherencetothewoundbedwas without exudatetransferlayerwaspreferredforthepreventionof or with dressing foam silicone thin a whereas hypergranulation, and pruritus ulcers, for suitable were layers contact silicone Soft forces. shear and friction from protection erosions, superficial gested thatthesilicone-basedfoamdressingscouldbeusedfor sug was Generally,it management. wound their in preferences jority ofauthorsreliedontheirclinicalexperienceandpatient care inEB.Results: had beenendorsedintherecentconsensusdocumentsonwound on the use of silicone-based dressings and fixation devices which This isaliteraturereviewsummarisingthepublishedevidence trauma and coverage of existing blisters. been demonstratedtobesuitableforEBbothprotectionfrom have devices fixation and dressings silicone-based Atraumatic be often avoided via the appropriate management of blisters. can which complications common are inflammation chronic and scar formation with subsequent deformities due to repeated trauma in the management of EB. Secondary infections and malignancies, solutions, pain-free daily wound care remains to be a cornerstone 42 dence Strategist,Mölnlycke® Health Care, Gothenburg, Sweden, Health Care, Gothenburg, Sweden Molnlycke® Health Care, Gothenburg, Sweden, MD, GlobalMedical Affairs and Safety Manager, Mölnlycke® Ph.D., Clinical Development Manager andEvidence Strategist, 4 EB2020 1 1 , JaneClapham st WorldCongressonEpidermolysisBullosa Due to the rarity of the condition, the ma the condition, the of rarity the to Due 3 Clinical Development Manager andEvi 2 Materials & methods: Patients were ,Viktoria Körner Materials & methods: 3 Nineteen patients , andUlanaPaw- 2 Lead EBNurse - - - - - 1 Paracelsus MedicalUniversitySalzburg, Salzburg, Austria Diem Austria, HOMOZYGOUS STATUS AND A MUTATION C.425A>GMIMICKING HEMIZYGOUS DELETIONOF COL7A1 BULLOSA DUE TO ALMOST COMPLETE RECESSIVE DYSTROPHICEPIDERMOLYSIS P38 with theneedsandwishesofusers. different dressingsinordertoensurethatdressingchoiceisaligned highlight theimportanceofunderstandingdesignfeatures respondents perform well and are well tolerated. The findings also that the silicone-based dressings and fixation devices used by the patients withJunctionalEB.Conclusions: dressing formoderatelyexudingwoundshavingcausedpainin foam silicone a of reports 2 were there however, tolerated, well were perceivedbyalluserstobeverygood. All dressingswere Withcapabilities absorptive their dressings, absorbent to respect to beeasyuseandcompatiblewithothertopicaltreatments. hours (average 1 to 2 hours). In general, the products were reported taken toundertakeadressingchangerangedfrom5minutes4 per day up to once a week (average 1-2 per day). Length of time bandage. Reported dressing change frequency ranged from 4 times over half (53%) of the respondents had used an elasticated tubular ne-based foam dressing had been used by 17 (89%) patients. Just BULLOSA USINGINTRAVENOUS FERRIC IN ADULTS WITH SEVEREEPIDERMOLYSIS TREATMENT OF MULTIFACTORIAL ANAEMIA P39 detailed study to define the breaking points is currently ongoing. covering COL7A1intheliteratureofepidermolysisbullosa. A from exon3to118. Herewithwereportthe3rdmicrodeletion DNA revealedapaternallyderivedhemizygousdeletionspanning (MLPA) copynumberanalysisfromthepatient´s andparent´s Finally,letion. amplification probe ligation-dependent multiplex narrowing theregioninbetweentobeashortpartofUPDorde heterozygosity, showed software Mapper Gene the using RFLP Analysis ofmicrosatellitemarkersencompassingCOL7A1by a paternity test confirmed the affiliation of the child to the father. in hermotherandwildtypethefather. The implementationof heterozygous were which 84, exon in c.6654C>G SNP a and 3 gene variants, the well-known hotspot mutation c.425A>G in exon cing confirmed by Sanger sequencing identified two homozygous homozygosity isusuallyregardedasUPD.NGSebpanelsequen deletion. Genetransmissionfromonlyoneparentalpartleadingto question ofbeinguniparentalisodisomy(UPD)orahemizygous resulted inadiscrepancyofCOL7A1genotypingandraisedthe 3-year oldpatientofan Austrian familydiagnosedwithRDEB mutations intheCOL7A1gene.Mutationanalysisof a meanwhile rare heritable blistering skin condition caused by loss-of-function Results: 5 Alfred Klausegger ne, University ofSalzburg, IgnazHarrer-strasse had used a soft silicone wound contact layer, whereas a thin silico (11%)2 Only respondents. patients the by used been had survey diagnosed withKindler’s syndrome. All productsincludedinthe with Junctional EB, (16%) and 10 3 (53%) with simplex, Dystrophic EB. EB None was with diagnosed were respondents Six (32%) female. were (68%) 13 and male were respondents (32%) logy, University Hospital of the Paracelsus Medical University, 0 EB House Austria andDepartmentofDermatology Allergo - 2 0 Salzburg,0 Austria, 1 , GabrieleSander 3 Recessive dystrophicepidermolysisbullosa(RDEB)isa Division ofClinical Genetics,DepartmentofPediatrics, 1 , NiklasJeschko 2 3 Interfaculty DepartmentofLegalMedici , DieterKotzot 1 , JanCemper-Kiesslich 3 , JohannW. Bauer The surveyindicates 79 , 5 0 2 0 Salzburg, 1 2 , Anja - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV tion, Milan,Italy kind so far. To fill this gap, the Italian EB registry Foundation registry EB Italian the gap, this fill Tofar. so kind in Italy, there has not been a systematic collaborative effort of this initiative of researchers as well as patient organizations. However, ral EB patient registries have been established in other countries by determinant for successful translational research. Therefore, seve bullosa (EB). In the field of rare diseases, registries can be a major for targeted studies hindertherapydevelopment forepidermolysis subpopulations identify to difficulty the and dislocation, graphic Introduction & objectives: The reduced patient number, their geo Michela Brena AFFECTED BY EPIDERMOLYSIS BULLOSA THE ITALIAN REGISTRY FORPATIENTS P40 to laboratoryandclinicalresponse. 100-110 g/l in this patient group, repeated 3-4 monthly according IV FCM as first-line treatment for anaemia with Hb levels below levels inpatientswithEB-associatedanaemia. We recommend maintenance therapyresultedinanoverallimprovementHb tions of retrospective review, our results suggest that IV FCM as included recessive dystrophic EB (RDEB) ( multifactorial anaemiaweretreatedwithIV FCM.EBsubtypes mean age35.2(17-71)years)withsevereEBcomplicatedby and MicrosoftExcel.Results: collection andstatisticalanalysiswereconductedusingSPSS-V.25 Data 2019. January and 2009 January between seen EB severe in maintaining haemoglobin (Hb) levels ≥ (FCM) carboxymaltose ferric IV periodic of safety and efficacy the investigate to study institution single retrospective, vational, ropoietin (EPO).Materials&methods:We conductedanobser intravenous (IV)ironinEBpatientswithout concurrent eryth of use the on evidence or anaemia, of management on practice has variableabsorption. There islimitedevidencesteeringbest iron supplementationmaycausegastrointestinalsideeffects and impacts onqualityoflifeandmayimpairwoundhealing.Oral factor. contributing significant a is deficiency Anaemia Iron pes. is multifactorialandacommoncomplicationinseveresubty Introduction &objectives: (EB) bullosa Anaemia inepidermolysis A. Alheggi OBSERVATIONAL, RETROSPECTIVESTUDY CARBOXYMALTOSE: A SINGLEINSTITUTION, and StThomas’ NHSFoundationTrust, London,UK 1 Mellerio 1 Sophie Guez Paediatric Highly IntensiveCare Unit,Milan,Italy, FCM whichwaswelltolerated.Conclusions:Despitethelimita unlike efficacy, poor or effects side to due (21.4%) patients 14 of 3 in discontinued was sucrose iron Parenteral g/l. 100 below initial improvement of mean Hb but levels remained persistently 120 g/l. In contrast, treatment with IV iron sucrose resulted in an 12 post3rdinfusionwhenthemeanHbpre-infusionwasabove week from apart significance, statistical achieved level Hb in levels were maintained ≥ improved. levels Hb Hb FCM, mean of infusion, initiation After blood transfusionatsomestage. At eachtimepointafterFCM UK Limited). Additionally, 5 of these 14 patients (35.7%) required had previously received IV iron sucrose (Venofer®, Vifor(32.5%) patients Pharma Fourteen infusions. 6 to up received (58%) 25 if indicated. All patients received at least one infusion of FCM and baseline andreceivedrepeatinfusionsaftera12-16weekinterval UK Limited)infusionaccordingtoHblevelandbodyweightat (n (DDEB) (n St John’s Institute ofDermatology, Fondazione IRCCSCa’ Granda OspedaleMaggiore Policlinico, = 2). All patients received IV FCM (Ferinject ®, Vifor Pharma 1 1 , J.A.McGrath = 1 3) and generalized intermediate junctional EB (JEB-I) 3) and generalizedintermediatejunctionalEB(JEB-I) 1 , Gianluca Tadini 100 g/l in all patients. The improvement 1 , L.Hubbard Forty-three adults (60.5% female; (60.5% adults Forty-three 1 , Paola Marchisio 2 Dietetic Department, Guy’s 2 , D.T. Greenblatt 100 g/l in patients with n

=

38), dominant DEB 1 2 , Cinzia Pilo REB Founda- 1 andJ.E. 2 ------, disseminating dataandnewknowledge. ERN-Skin. Finally, this resource will be a means for sharing and with specifically and (ERN), Networks Reference European the nationally and internationally, where it can foster exchanges with for collaboration among physicians, researchers and patients both platform a become to aims Registry EB Italian the Furthermore, research aswelltherecruitmentofpatientsinfuturetrials. counselling. It will also be instrumental to foster translational correlation and improve diagnosis, disease course prediction and erapies. A functional EB Registry willenable genotype-phenotype and improvepostmarketingsurveillanceofdrugsoff-label th of diseases, facilitate clinical, epidemiological and basic research understanding better a allow registries data, patient of collection systematic EB centreshavebeenenrolled.Conclusions:Through approximately 1/3 of thepatients already treated in the involved new researches.Results: patient population. This knowledgewillbeparamounttoplan will informabouttheepidemiologicalandclinicalfeaturesof Life questionnaires. Aggregated data analysed by means of queries, of Quality hoc ad in fill and access patients where Portal Patient the highest standards for data protection. It is equipped with a sites. The registry complies with theGDPRregulation and ensures ber ofpatientsandtoincreasecollaborationamongparticipating of treatment, with a maintenance during follow-up, without requi end the at lesions the of resolution complete a to leading weeks, wounds. The newbornhasbeentreatedweeklywith CBPG for4 the of improvement significant a with exudate, and bleeding reducing in helpful was use its but lesions, granulating chronic, follow-up. On the other side, CBPG was not equally effective on comparing tostandardmedicationsandamaintenanceduring healing faster with re-epithelisation, skin and recovery complete wounds had a significant benefit from the CBPG application with different,acute were lesions: results the of age the on depending often forcing the newborn’s foot into a bent pose. uterus, in friction to prone position a is it since patients DEB in deep skin ulcers localized on both shins, a site frequently observed days. 3 had every newborn or The weekly 8), to 3 from (ranging by DEB.PatientsweretreatedwithseveralCBPGapplication our departmenttreated15patientsandanewbornbabyaffected 2014-2018 in patientswithDEB.Materials&methods:During ulcers skin of treatment the for neonates, healthy,term of blood (CBPG), a novel blood component obtained from umbilical cord among monthsoryears. We usedallogeneiccordbloodplateletgel with spontaneous resolution within few days or weeks, or chronic typically located on friction-exposed areareas. Lesions can be which acute, lesions, clinical of severity the determine mutation dominant or recessive trait. Both type of inheritance and specific caused by mutation in collagen (DEB), VII bullosa gene, inherited epidermolysis as an dermolytic autosomal is (EB) bullosa lysis Introduction &objectives: The mostcommonformofepidermo Paediatric HighlyIntensiveCare Unit,Milan,Italy Fondazione IRCCS Ca’ GrandaOspedale Maggiore Policlinico, Sophie Guez Michela Brena, Gianluca Tadini, Paola Marchisio, Paolo Rebulla, EPIDERMOLYSIS BULLOSA CORD BLOODPLATELET GEL INDERMOLYTIC P41 national clinicalcentresinordertoerollthehighestpossiblenum were involved. However, REB is seeking collaboration from other collection from EB patients in Italy. So far, two Italian EB centres multicentre clinical study that relies upon a comprehensive data country. the in registry EB multi-stakeholder and multicentre first the been workingwithmajorclinicalcentrestosetupandmanaging (REB) was established in 2017 by Debra Italy and since then has Materials & methods: The REB developed a longitudinal, Enrolment started in 2019 and, to date, to and, 2019 in started Enrolment Acta DermVenereol Suppl220 Results: Posters Clinical Clinical 43 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta EPIDERMOLYSIS BULLOSA: A CLINICAL TOOL THE ASSESSMENT OF HANDCONTRACTURESIN P43 be usedtoguidetreatment. These findings show a predictable course of progression that may age ofonsetandthesequencehandcontracturedevelopment. validated, our results provide more detailed information about the limitations ofasmallsamplesizeandusingtoolthatisnotyet Hand ContracturesinEpidermolysisBullosa(ACE).Despitethe hand contracture progression inchildren using the Assessment of rapidly. more progress and later emerge contractures flexion Finger contractures developnextandalsoprogressslowlyovertime; are subtle and progress slowly over time; Thumbs adduction first, Webdevelopment: develop contracture contractures space of sequence the in trend a identified we Furthermore, cases. of majority the in components three all involving HDG, severe or moderate a had children the of all years, 12 age severe; At and moderate mild, between varying HDG a had children the of all cases; of years,majority 6 the age in At contractures space web involving HDG, mild a had children the of half years, 2 age At development: At birth, none of the children had hand contractures; identified four significant time points regarding hand contracture 2019. and Weand (HDG) Grades Deformity Hand the analysed 2010 between females) 13 males, (12 years 0-16 aged children present theresults.Results: the overallhanddeformity. Descriptive dataanalysiswasusedto Deformity Gradewhichgivesaneasilyunderstoodimpressionof moderate orsevere. They were alsocombinedtoprovideaHand dactyly), finger flexion and thumb adduction were scored as mild, (pseudosyn spaces web contractures, component typical three had the ACE administeredbyanOccupational Therapist. The and regardlessofconservative hand therapyroutines. All patients surgery hand of history a without RDEB, generalised severe of cialist paediatricEBcentre. We includedchildrenwithdiagnosis retrospective casenotereviewofpatientswhoattendedourspe in childrenwithRDEB.Materials&methods:We carried outa ding ageofonsetandsequencehandcontracturedevelopment (ACE) routinely in clinical practice. We report our findings regar the Assessment ofHandContracturesinEpidermolysisBullosa data ontheprogressionofhandcontracturesislimited. We use impact onfunctionandqualityoflife.Systematicallyrecorded epidermolysis bullosa(RDEB)develophandcontractureswhich Introduction &objectives:Childrenwithrecessivedystrophic gery Consultant Paediatric Dermatology ConsultantsandGill Smith, Plastic Sur Martinez andGabrielaPetrof Nicky Jessop andCatherine Miller, Occupational Therapists, Anna EPIDERMOLYSIS BULLOSA CHILDREN WITH RECESSIVEDYSTROPHIC HAND CONTRACTUREDEVELOPMENT IN P42 tion intoneoplastictransformation. superinfections, retracting permanent scar development or evolu DEB patients, even in the newborn, in order to prevent fluid loss, CBPG isapromisingandsafeoptionfortreatingskinlesionsin patients’on impact positive a have conclusion, In life. of quality can significantly reduce the risk of neoplastic transformation and important topointoutthatevenapartialreductionoftheulcers been obtained on acute lesions rather than in chronic lesions, it is patients.Evenifthebestresultshave inDEB of skinlesions treatment topical the for CBPG of efficacy clinically and safety reasons. ring anyadditionalreconstructivesurgery foraesthetic/functional 44 EB2020 1 Conclusions: We havesystematicallygathereddataon Conclusions: The clinical results support the evidence on st WorldCongressonEpidermolysisBullosa We completed 186assessmentson25 - - - - - Chile, Santiago,Chile 1 G. Tartaglia BULLOSA PATIENT FIBROBLASTS MODELING FIBROSISINEPIDERMOLYSIS P44 of handcontractures. it hasthepotentialtobeusedreportonnaturalprogression ractures impactonhandfunctionandqualityoflife.Ifvalidated be used together with functional measures to report on how cont families makeinformeddecisionsabouttreatments.Itcanalso outcome measure following hand surgery. It helps clinicians and of handcontracturesinchildrenwithRDEB. It can beusedas an is aclinicaltoolthatcanbeusedforthesystematicassessment next stepinthedevelopmentof The ACE ACE. Conclusions: inter-rater foundgoodagreement. reliabilitystudy Validation isthe tive feedbackandsubsequentlymademinorimprovements.Our clinical team. From our survey of experts, we received construc to communicate an impression of overallhanddeformityto the the webspacecontracture. We usetheHandDeformityGrade for particularly assessments, existing than sensitive more is It astructuredmethodofadministration.a systematictoolwith with andwithoutahistoryofhandsurgery. We considerittobe the ACE routinelytomonitorthehandsofpatientswithRDEB reliability studyforthe web space component. Results: and clinical usefulness of this tool. We completed an inter-rater sensitivity content, the regarding Therapists Occupational and Dermatologists Surgeons, Hand of opinion expert the surveyed and patientsatisfactionwithhandfunctionappearance. We ACE also records wrist and forearm motion, splint and glove wear Grade togiveanimpressionoftheoverallhanddeformity. The these component scores are combined to provide a Hand Deformity Additionally,severe. or moderate mild, as graded is component Each adduction. thumb and flexion finger spaces, web ractures: in childrenwithRDEB.Itscoresthreetypicalcomponentcont practice toenablesensitivemeasurementofhandcontractures tool. Hand ContracturesinEpidermolysisBullosa(ACE)asaclinical assessment ofthewholehand. We introducethe Assessment of surgery. There isnowidelyacceptedclinicaltoolforthesystematic detect emerging contracturesorrecurrentfollowing tion contractures.Manyofthesemethodslackthesensitivityto adduc thumb and flexion finger (pseudosyndactyly), space web quality oflife. The literaturedescribesvariousmethodstoassess and function on impact which childhood, in deformities hand with recessivedystrophicepidermolysisbullosa(RDEB)develop Introduction &objectives: There iswideagreementthatpatients gery Consultant Paediatric Dermatology ConsultantsandGill Smith, Plastic Sur Martinez andGabrielaPetrof, Nicky Jessop andCatherine Miller, Occupational Therapists, Anna identified a number with potential therapeutic application. In application. therapeutic potential with number a identified and compounds FDAapproved 1,443 screen to model this used fibroblasts. RDEB primary by deposition ECM fibrotic have We work in the lab has developed a 3D tissue-engineering model of squamous cellcarcinomadevelopment andmetastasis.Previous tocutaneous itcontributes because patients concern inRDEB ted TGF-beta signaling, and tissue scarring. Fibrosis is also a major matrix (ECM) turnover, accumulation of fibrillar collagen, eleva extracellular excessive its to due disorder fibrotic a as classified be can disease, butterfly as known otherwise (RDEB), Bullosa Introduction &objectives:RecessiveDystrophicEpidermolysis CONTRACTURES FOR THE SYSTEMATIC ASSESSMENT OF HAND Jefferson University, Philadelphia, PA, USA, Department of Dermatology and Cutaneous Biology, Thomas Materials & methods: We developed the ACE through clinical 1 , I.Fuentes 1,2 , T. Webster 1 , A. South , A. 2 Fundación DEBRA 1 We use ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Trust, Hashimdeen measurements into knitted gloves. Use of the dressing glove fit took several iterations due to the difficulty of translating hand absorption andprovidemoreprotection. Achieving thecorrect Participants reportedathicker viscose materialcouldimprove Web spacesandwristfunction werealsomostlymaintained. sings; reducedskinmaceration; andimprovedskinappearance. improvement intheirexperienceofwearingandchangingdres study. Elevencarersalsoprovideddata.Participantsreportedan the completed four and glove dressing the with fitted were nine the HTO system.Results: being conductedinonecentrewithinaServiceEvaluationusing were usedtoassessperformance.Routineclinicalfollow-up is interviews telephone and t-tests unpaired measures, outcome recorded contemporaneous notes. Visual inspection of plotted of conventionalproductswerealsoself-reported.Participants use and frequency changes, mes). dressing Timehand for taken outco (secondary function hand and pain hand function, wrist webbing, finger of extent and outcomes); (primary condition experiences ofwearingandchangingdressingshandskin and uploaded to a Hand Therapy-Online (HTO) system included: measures, co-designed and validated with patients and clinicians process ofmeasurementandadjustment.Self-reportedoutcome with bespoke dressing gloves, manufactured to fit in an iterative Participants wereinvitedtoreplacetheirconventionaldressings hands orwereadvisedtorecruitedfromtwotertiarycentres. with RDEB(adultsandchildren)whoworedressingsontheir Participants use. dressing regarding preferences and skills tics, was conductedtoaccountfordifferences inclinicalcharacteris costs. evaluate theperformanceofnovelglovesandanalyse dermolysis Bullosa(RDEB). The objectiveofthisstudy wasto were co-designedwithpeopleRecessiveDystrophicEpi glove, web-spacer reinforced and glove dressing disposable a baggy andimpedehandfunction. To overcometheseproblems bulky, are Dressings tolerated. not often are contractures and Introduction & objectives: Current hand devices to delay webbing 1 T. Graham EPIDERMOLYSIS BULLOSA REINFORCED WEB SPACER GLOVEFOR UP OF A DISPOSABLEDRESSINGGLOVE AND PROOF OF CONCEPT AND CLINICAL FOLLOW P45 of fibrosisinRDEBfibroblasts. to further elucidate the intricacies behind the mechanism ofaction collagen’sfibrosis. in role behind complexities the into insight another offers which do, fibroblasts normal than collagen more secrete fibroblasts RDEB differed due to compound treatment; however, we also noted that in cellstreatedwiththeantineoplasticagent.Collagenlevelsalso phospho-AKT,and phospho-SMAD3 using pathways, signaling downstream targets ofthecanonicalandnon-canonical TGF-beta varying doses.Results: tion, we assessed proliferation and viability of each compound at addi In fibroblasts. normal and fibroblasts RDEB of treatment after markers fibrotic of profiles expression protein quantified courses, measured TGF-beta activation and collagen content, and action of these compounds we first performed dose-response time Materials &methods:Inordertoinvestigatethemechanismsof receptor inhibitor, an antineoplastic agent, and an integrin inhibitor. the TGF-beta positivecontrol. The threecompoundsareanicotinic observed three compounds that accelerated fibrosis compared with also we fibrosis, delayed that compounds identifying to addition King’s College London, 3 Materials &methods:AnN-of-1proofofconceptstudy Cardiff University 1 , S. Sooriah 3 and P. Grocott We notedanunexpecteddownregulationof 1 2 , R. Box Guy’s andSt. Thomas’ NHSFoundation Conclusions: Withaim we data, these Twelve participants were recruited, were participants Twelve 2 , T. Meydan 3 , P. Williams 3 , S. - - - - - clinical nurse specialists (CNS), dietitian, plastic surgeon, psy surgeon, plastic dietitian, (CNS), specialists nurse clinical patients The MDT includes consultant and trainee dermatologists, international some includes also cohort Wales,the and although England from predominantly service, the with registered are EB hospital services. Materials & methods: Currently, 480 adults with and is supported by domiciliary visits and collaboration with wider patient engagement and needs in mind, has improved access to care with designed RDC, The EB. with adults for care holistic cialist and houses an extensive multi-disciplinary team (MDT) for spe 2017 November in opened children and adults for (RDC) centre Introduction &objectives: The first purpose built UK rare diseases Guy’s andStThomas’ NHSFoundationTrust Clapham, CMackenzie,SWharton,Bloor K Snelson, A Downe,JEMellerio, JA McGrath,DT Greenblatt, J EPIDERMOLYSIS BULLOSA (EB) AN ENHANCEDMODEL OF CAREFOR P46 evaluation andcostanalysis. long-term record, patient-clinician shared a supports collection are availablethroughthebespokesupplychain.Continualdata sing gloveforpatientswhocouldwearthegloves.Bothgloves is underpinnedbydomiciliaryvisits bytheCNSteam. appropriate services within the MDT and beyond. Hospital activity manner. Diseasemanagementisoptimisedbycollaboration with access to a wide range of specialists in one place in a time efficient provided in a purpose built environment. Patient benefits include the RDCactivityhasincreased andtheuniquemodelofcareis 2019) Sept – 2018 (Sept vice 17 patientshavetransitionedfromthepaediatrictoadultEBser • CNSHomevisits212 • Podiatry(twicemonthly)312 • Ad Hocreviews116 • Standardoutpatients(monthly)319 • Skype(1-2permonth)39 • CNSled(weekly)85 • Mini-MDT (1-2permonth)106 • ComplexMDT (monthly)86 patients seen(Nov2017-Sept2019). and partnershipworkingwiththepatientcarers.Numberof symptom management, enabling effective therapeutic relationships CNS home visits to complex patients forskin assessment and cancers. An essential component ofthis holistic model are regular hoc reviewe.g.ofunwellpatientsorforpossibleskin ad as well as appointments ophthalmology and dental reviews, dietetic psychotherapy,therapy, hand dilatations), oesophageal surgery, cancer surgery, hand for (e.g. admissions urgent and elective supports service the addition, In clinic. Skype CNS-led clinic; twice monthly all day EB podiatry clinic; • twice monthly EB CNS-led MDT;weekly wider • the of members select see to • once to twice monthly mini-MDT clinic for 8 complex patients monthly MDT clinicfor6complex patientstoseethewholeteam; • patients); (30-40 clinic outpatient standard monthly • include: are triagedaccordingtotheirMDT needs andcomplexity. These The RDChouses avariety ofdifferent clinics types where patients the centre to record clinical activity and patient contact. and dedicatedRDCstaff. Datahasbeencollectedsinceopeningof managers support community UK Debra co-ordinator, EB tists, ophthalmologist, palliative pain consultant, radiologists, anaesthe dentist, podiatrist, physiotherapist, therapist, hand chotherapist, This study provides early proof-of-concept for the novel dres outcome measureswithintheServiceEvaluation.Conclusions: Five additionalpatientsadoptingtheglovesareself-reporting completing the study wanted to remain in the dressing gloves. two becauseofmorefrequentdressingchanges. All participants was costneutralfortwoparticipantsandincreasedtheother Conclusions: Sincetheopeningof Acta DermVenereol Suppl220 Posters Results: 45 - - - - -

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta G Webster Reinhardt University,Salzburg, Austria, and Allergology, University Hospital of the Paracelsus Medical lecular Therapy ofGenodermatoses,DepartmentDermatology ris Rebolledo-Jaramillo guera bauer 1 Ignacia Fuentes EPIDERMOLYSIS BULLOSA PATIENTS IMMUNE CELL PROFILINGOF WOUNDS FROM P48 But toreachmaturitymuchmorefundingisneeded. steps havebeenmade. The projectisadvancingandgrowing up. first The EB. for medicine new a into candidate drug promising to providethetechnicalexpertiseandfundingturnthis Now ittakesaconcertedmultidisciplinaryeffort bymanyparties ceutical industry. For losartan for EB, only the former is fulfilled. as oneconomictermsinordertoattractfundingbythepharma candidates need to convince on a medical/technical level as well development andapprovalprocess.Conclusions:Promisingdrug fee reductionsandsupportby the agencies along the regulatory signation hasbeenobtainedfromFDA andEMA. This provides sought fortherequiredtechnicaldevelopment.Orphandrugde is funding and defined been have requirements User needed. is formulation new,easy-to-swallow a hurdle: new unexpected an formulation of losartan is no longer available in the market, posing – nowfundingisneededforthisdecisiveclinicaltrial. A pediatric A clinicaltrialprotocolandastudybudgethavebeendeveloped and aid in planning of a larger confirmatory, pivotal clinical trial. data safety Salzburg,important provide will results Austria. The Freiburg,in centers EB the at ongoing currently is and Germany needed. A first clinical trial of losartan in EB, funded by DEBRA, investment intoclinicalstudiesandalternativefundingsourcesare an recoup to expect les: Withcannot companies expired, patents hurd economic new poses however,fact – this hypertension) of is anestablishedmedicine(availableastabletsforthetreatment fewer technical hurdles compared to other, novel treatments as it medicine (manufacturingandcontrols).Results: new the of quality the and assessment, risk vs benefit positive a Such approval will confirm a high standard of medical evidence, sought: are EMA) Agency, Medicines European the and FDA objective. Approvals byregulatoryagencies(inparticulartheUS A multidisciplinaryteamhascometogethertoworktowardsthis children. DEB in scarring fibrotic of tion preven the particular in EB, of treatment the for efficacious and of losartanandtocreatemedicalevidencewhetherissafe fusion ofdigits. Ourobjective is to develop a pediatric formulation prevented and scarring fibrotic reduced losartan EB, dystrophic with secondary scarring and fibrosis. In a mouse disease model of disease blistering skin a (EB), bullosa epidermolysis dystrophic tion to treat hypertension, has shown promise for the treatment of medica well-established a Losartan, Introduction & objectives: Dimitra Kiritsi TO RAISE A CHILD’ LOSARTAN FOREB,OR‘IT TAKES A VILLAGE P47 46 1 GmbH ([email protected]), Heather IRishel Anja Diem Department ofDermatologyand Allergology, ParacelsusMedi - lo, Santiago,Chile, Facultad de Medicina Clínica Alemana, Universidadde Desarrol- DEBRA Chile,Santiago, Medical Center – University of Freiburg, 3 1 ,*, Andrew P. South , Yessia Hidalgo EB2020 1 3 11 , LeenaBruckner-Tuderman 4 , AlfredKlausegger , Marco Prisco 1 , Tobias Zahn 1,2 9 , M.Peter Marinkovich st , ChristinaGuttmann-Gruber WorldCongressonEpidermolysisBullosa 3 EB House Austria, Research Programfor Mo- 5,6 2 , Pilar Morandé , MaríaJoaoYubero 11,13,14 11 , LuisH.Eraso 2 4 3 , FrankHoffmann * B House Austria, OutpatientUnit, , GlendaCofré-Araneda 2 3 Centro deGenética y Genómica, Midas PharmaGmbH 1 1 9,10 , FrancisPalisson 2 3R Pharma Consulting Materials &methods: 12 , Joyce Teng , Josefina Piñon Hof- Piñon Josefina , 1,7 , RaymondJCho 3 , Birgit Tockner 3 , SigridSaaler- Losartan faces 1 9 , OlgaFi- , Timothy 1,7 , Bo- 8 3 - - - - - , , Aida Lugo-Somolinos Dermatology, SanFrancisco, CA, United States, Consortium forRegenerative Medicine, Santiago Hill, NC, USA, [email protected]. *Theseauthorscontributedequally ted States.Correspondence: [email protected] or cer Center, ThomasJefferson University, Philadelphia, PA, Uni- CA, Department, Stanford University School of Medicine, Stanford, sity, Philadelphia, PA, United States, dation Trust, London, England, John’sInstitute ofDermatology, Guy’sand St.Thomas’ Foun- NHS 1 Paris, France, rell Also, after special culturing conditions, highly proliferative ad proliferative highly conditions, culturing special after Also, consisting ofaheterogeneousmixtureskinandimmunecells. cells from wound dressings (ranging from 0.08 – 620x106 cells), Results: host cellularroleinwoundhealingand2)diseasediagnosing. the profile 1) to method sampling noninvasive a as patients EB from dressings wound of use the investigated we study, this In explored inthecontextofwoundresolution.Materials&methods: been not has dysregulation immune host of impact the wever, Ho disease. inflammatory and skin heritable a of combination cancer. The current state of research points towards EB being a and infections systemic as such manifestations, clinical deadly– extremely painful, are the starting point to other more severe –and blisters can patients, develop into EB nonhealing wounds, severe which besides In being trauma. minimum with blisters causing group ofgeneticdiseasescharacterizedbyexcessiveskinfragility Introduction & objectives: 11 6 2 Joyce Teng SIMPLEX: RESULTS OF A PHASE 2STUDY TREATMENT OF EPIDERMOLYSIS BULLOSA DIACEREIN 1%OINTMENT FOR THE P49 as individualswithEpidermolysisbullosa. better clinicalmanagementofpatientswithchronicwoundssuch cell infiltrate, bacterial infection and wound healing may lead to a skin wounds.Understandingtherelationshipbetweenimmune of content cellular the profile to platform a provide and nostics wound bandagescanbeusedfornoninvasivemoleculardiag EB patients.Conclusions: Together ourdatashowthatdiscarded status ofagivenwoundtobetterunderstandresolutionin we areactivelycorrelatingthesepopulationsubtypesandhealing indicating differential immune cell infiltrate in wounds. Currently CD3+ T-cell (ranging from 0 to of 78% of CD45+ cells) and others, representation minor some populations, CD45- and CD45+ distinguish to able is technique our suggests Cytometry flow by diagnosis forpatients.ImmunePhenotypingoftheisolatedcells molecular accurate DNAin genomic resulting isolated, be could herent fibrocyte-like populations were obtained and NGS quality University, Philadelphia, PA, UnitedStates, Joan CenterforFibrotic DiseasesResearch,Jefferson Thomas Jefferson University, Philadelphia, PA, UnitedStates, don, England, Spellman Alemana, Universidad de Desarrollo, Santiago, Chile, USA, IL, USA, IL, cal University, Salzburg, Austria, Cells forCells,Santiago,Chile, Northwestern University, Feinberg SchoolofMedicine, Chicago, Stanford University, School of Medicine, Palo Alto, CA, USA, Dermatology andCutaneousBiology,Jefferson Univer Thomas 4 , JemimaE.Mellerio 10 4 Dermatology Service, VA Medical Center, Palo Alto CA, St. George Hospital, UNSWSydney, Sydney, Australia, 3 We were able to isolate significant numbers of viable of numbers significant isolate to able were We 11 University ofColoradoSchoolMedicine, Aurora,CO, 1 , Amy S.Paller 7 8 Great Ormond Street NHSFoundationTrust, Lon- University of North Carolina-Chapel Hill, Chapel 9 Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, 8 , EliSprecher 5 , Christine Bodemer 2 Epidermolysis bullosa or EB, is a is EB, or bullosa Epidermolysis , Anna L.Bruckner 6 Hôpital Necker-Enfants Malades, 7 5 Facultad deMedicinaClínica Consorcio Regenero, Chilean 9 , JohannW. Bauer 12 Vascular Medicine, Thomas 14 Sydney KimmelCan- 6 , Anna E.Martinez 3 , DedeeF. Mur 9 762 Dermatology 0 10 13 157 , MaryC. Joel and , Chile, 8 UCSF 5 St. 7 - - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV College, Vellore, Tamil NaduIndia. Salzburg,Salzburg, Austria, arm and hand. Then the fingers of 2 or 3 more gloves are snipped an simulate to cardboard the of end one to fitted and gauze with elastic bandsplacedaroundthe tube. A surgical glove isstuffed writing pad (approximately 21 x 30cm), is rolled lengthwise and A4 an of back the as such cardboard, of length & methods:A which canbecreatedwithreadily availablematerials.Materials teaching aid simulating a patient’s forearm with multiple blisters thetechnique onpatientswehavedevisedasimple demonstrating realistic. sufficiently avoid not To is but training for blisters late patients andcaregivers.Bubblewrapissometimesusedtosimu introducing infection is essential but can be a major challenge for place. Learning how to burst blisters safely, in painlessly left and be should without roof blister The fluid. the absorb and out wick by gravityifpossible.Sterilegauzeorcleantissuecanbeusedto freely, drain to fluid allowing blister the puncture neatly assisted to theskinavoidpainfulcontactwithblisterbaseandshould needle, scalpel or scissors. The instrument should be kept parallel cleavage. To prevent this, blisters must be drained using a sterile has formed it readily enlarges as the fluid seeps along the plane of a blister Once fluid. interstitial with fills which space a creating adhesion, skin impairs weakness genetic the because (EB) losa Introduction &objectives:Blistersoccurinepidermolysisbul Departments ofDermatology Dharshini Sathishkumar PROFESSIONALS EPIDERMOLYSIS BULLOSA FORPATIENTS AND A NOVEL BLISTER-BURSTING TEACHING AID IN P50 at higherconcentrationstooptimizeitsefficacy. lesions, compared to vehicle, supporting further study of diacerein 1% ointment achieved a ≥2-point reduction in IGA score for EBS diacerein receiving patients of proportion larger a achieved, not was significance statistical Although in severity. Conclusions: mild were effects adverse drug−related study all tolerated; well the control group. Diacerein 1% ointment was generally safe and of 23.1% and group 1% diacerein the of 39.3% for reported was (26.9%), but not significantly (p the diacerein 1% group (42.9%) compared with the control group achieved successontheIGA keysecondaryendpointwashigherin but not significantly (p (53.8%), group control the in than (57.12%) group 1% diacerein the in greater numerically was BSA) EBS in reduction (≥60% The proportionofpatientswhoachievedtheprimaryendpoint score for the assessed area, were evaluated over 8 weeks. 2-point reductionintheInvestigator’s Global Assessment (IGA) (BSA) area of EBS lesions, and the key surface secondary endpoint, at least a body in reduction ≥60% a endpoint, primary The (n 1% diacerein to EBS severe to moderate confirmed genetically with patients 54 zed, double-blind,vehicle-controlled,Phase2studyrandomized 1% ointment vs vehicle in EBS. diacerein of efficacy the compare to was study this of objective viously beenshownto reduceblistering inpatients with EBS. The pre has IL-1β, of inhibitor an ointment, 1% Diacerein EBS. of 1β), a pro-inflammatory cytokine, is implicated in the pathogenesis pain and itch management. The expression of interleukin-1β (IL- Current treatment of EBS includes conventional wound care, and skin and other tissues, resulting in recurrent blisters and erosions. is araregeneticdisordercharacterizedbystructuralfragilityofthe Introduction &objectives:Epidermolysisbullosasimplex(EBS) Israel, sippany, NJ,USA hu 2 , JamunaPannerselvam 10 University Hospitalofthe Paracelsus Medical University = 28) orvehicleointment(n = 1 , Ananda Ruby Jacob 0.9666). The proportion of patients who 2 11 Castle Creek Pharmaceuticals, Par 1 andNursing Materials & methods: A randomi = 0.2861). An IGA score of 0 or 1 2 , ChristianMedical 2 , Angel Gnanamut- , Angel = 26) oncedaily. Results: - - - - - Departments ofDermatology Dharshini Sathishkumar FROM INDIA DUE TO PLECTIN MUTATION -CASEREPORT BULLOSA SIMPLEX WITH NAIL DYSTROPHY AUTOSOMAL RECESSIVEEPIDERMOLYSIS P51 EB professionals. with surgical interventions. We hopethismodelwillhelpfellow associated anxiety the removing people, young and children for ting and using the model can be entertaining as well as instructive plectin phenotype. the of complexity the emphasises and mutations, plectin to due this isonlythesecondcasereported ofEBSwithnaildystrophy knowledge, dystrophy infuture.Conclusions: Toour of best the regular followuptoassessifshe willdevelopsignsofmuscular tion inourpatientisunknown and thechildwillbekeptunder muta the of distribution tissue However,the muscle. striated in exon 1affecting theplectin1A isoformwhichisnotexpressed with naildystrophydescribedinliterature(1)hadamutation to counseltheseparentsaboutfuturerisk. The singlecaseofEBS systemic manifestations due to plectin mutations makes it difficult due toplectinmutations. The somewhatvariableoccurrenceof dystrophy nail with EBS recessive autosomal is diagnosis final the Thus, subtype. Ogna dominant the excluded Homozygosity pyloric atresiaormusculardystrophy(normalmuscleenzymes). #131950. On review at 9 months, there was no clinical evidence of type Ogna EBS and #612138 atresia pyloric with EBS #226670, EBS with nail dystrophy #616487, EBS with muscular dystrophy mutations: plectin by caused phenotypes EBS 4 lists omim.org https://www. database OMIM The gene (PLEC).Discussion: Arg1627TER) homozygousmutations inexon31oftheplectin neration sequencingwasundertaken. This revealed c.4879C>T(p. began tothrive. This made JEB lesslikelyandthereforenextge she and significantly symptoms airway and reflux her improved signs of reflux. Subsequent treatment with a proton pump inhibitor erosions confined to the ary-epiglottic folds and vocal cords with sultation wassought.Cautiousnasopharyngolaryngoscopyshowed bullosa (JEB).Inviewofthehoarsecryotorhinolaryngologycon clinical picturewasinitiallysuggestiveofjunctionalepidermolysis underweight butotherwisewellanddevelopingnormally. The unaffected. There was no relevant family history and she appeared plate onmanydigits. The oralandgenitalmucosae andeyeswere nail the of separation and thickening with feet and hands face, reflux.and the involving erosions few a had she presentation, At skin from birth. She also had progressive hoarseness, with cough the of blistering easy with presented parents, consanguineous second-degree of born first girl, 3-month-old ACase report : EBS. present acaseillustrating the broad phenotype of plectin-related plex subtypes of basal epidermolysis bullosa simplex (EBS). We last 20 years plectin has emerged as a gene responsible for com- tian MedicalCollege,Vellore, IndiaResults:Introduction: Inthe blisters, and empowers individuals in self-care. Furthermore, crea real-life for substitute low-cost effective, an provides It blisters. EB burst to how groups professional and families individuals, have foundthisblistermodeltobeextremelyusefulinteaching and can be used topractice bursting blisters. forearm withmultipleblistersiscreated(photographattached) the tube and taped in place. Thus, a model simulating a hand and balloons areinserted. The threadsarepulledtotheopenendof in thecardboardthroughwhichthreadshandtiedendsof gloves can be used to cover the cardboard tube. Slits are made these of parts wrist remaining The balloons. water-filled small off, filled with water and the open ends tied with thread to create 1 , NainaEmmanuel 1 andOtorhinolaryngology Acta DermVenereol Suppl220 2 , RenuGeorge We Conclusions: We Posters 2 , Chris- 1

47 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Harper Price, MD, MoiseL.Levy, MD,Lawrence A. Schachner, MD, F.Eichenfield, Lawrence MD, Powell, Julie MD, McCuaig, MD, Kimberly D. Morel, MD, Amy S. Paller, MD, Catherine C. MSc, Karen Wiss, MD,KristenP. Hook,MD,LauraE.Levin, Y. Tang, MD,PhD,Irene Lara-Corrales,MD,Elena Pope, MD, les, BA, Anna L.Bruckner, MD,MSCS,PhuongKhuu,Jean Gregory S. Phillips, BS, Bret D. Augsburger, BA, Kathleen Peop- LARGE EPIDERMOLYSIS BULLOSA COHORT IN ACHRONOLOGY, CONCORDANCE AND PATTERNS,TESTING DIAGNOSTIC P53 cm 70 to up wounds to B-VEC administered were and study rection. Two additionalpatientswereenrolledontothePhase2 biopsies oftheB-VECtreatedsitesdemonstratemolecularcor in zone membrane basement the at fibrils anchoring of presence COLVIIlinear robust closure, wound to addition and expression strating the ability of B-VEC to treat difficult chronic wounds. In demon closure, complete following evaluation months) (3 days re-administration. This woundcontinuestobeclosed attheninety 90-day timepoint - 100% wound closure was achieved following did notclosecompletelywasre-administeredwithB-VECatthe the woundscontinuetobemonitored. The onechronicwoundthat and evaluation, 90-day the at 100% closed remained wounds 6, months) and 174 days (6.2 months). In the Phase 2 study, 5 out of (6.6 days 184 was up follow last the of as closure wound 100% Phase 1, the duration of wound closure on two patients following treated wounds (7 out of 8) was 20.14 days (median 20 days). In (100%). completely The average time to 100% wound closure on all KB103 closed KB103 with treated wounds 8 of out 7 1/2, in allsixB-VECadministeredpatients.InthecombinedPhase tolerated andnoB-VEC-relatedsafetyeventshavebeenreported vivo approachtoRDEBgenecorrection.B-VEChasbeenwell- novel a of demonstration successful continued report we trial, this updateoftheongoingPhaseI/IIplacebocontrolledclinical correction. molecular and closure, safety,wound for to inability to travel to the clinical site. Subjects were monitored as onepatientinthePhaseIItrialdroppedoutofstudydue placebo analyzedagainst were Eight(8)ofthetenwounds B-VEC. enrolled in Phase II, and a total of ten wounds were administered RDEB patientswereenrolledinPhase1andfour patient wounds in anoutpatient setting. Materials & methods: Two taining twofunctionalCOL7A1genesapplieddirectlytoRDEB a topically administered, replication-deficient HSV-1 vector con Introduction &objectives:Bercolagene Telserpavec (B-VEC) is 2 1 M.P. Marinkovich BULLOSA (RDEB) RECESSIVE DYSTROPHICEPIDERMOLYSIS TELSERPAVEC, B-VEC)INPATIENTS WITH A TOPICAL GENETHERAPY (BERCOLAGENE P52 RESULTS FROM A PHASEI/IISTUDY OF G., Pasmooij, M. H., A. H. Pas, H., Lemmink, M., Nijenhuis, B., K. Gostynska, 1. Reference multicenter Phase3trialisplannedforlate2019. can beeasilyadministeredinbasicclinicfacilitiesworldwide. A safe andeffective approachtoRDEBmolecularcorrectionwhich novel, a demonstrate studies clinical I/II Phase the from results Overall, on-going inthesetwoadditionalpatients.Conclusions: to study chronic wounds in further detail. The Phase 2 study is Krishna www.medicaljournals.se/acta 48 Krystal Biotech,Inc,Pittsburgh, PA, UnitedStates Dermatology, Stanford University, Stanford, CA,UnitedStates, Molec Genet.2015;24(11): 3155-3162. Hum simplex. bullosa epidermolysis skin-only autosomal-recessive causes 1a, Lang et al. Mutation in exon 1a of PLEC, leading to disruption of plectin isoform EB2020 1 st 1 WorldCongressonEpidermolysisBullosa , Schuyler Vinzant 2 , Pooja Agarwal , Results: 2 , Suma In in - - - 2

discordant (2%). Similarly, IFM results were equivocal, concor equivocal, were Similarly,results (2%). IFM discordant largely equivocal (36%) and concordant (28%), but rarely frankly EM andgeneticanalysisamong163patientsshowedtobe EM andIFMin2008(Figure).Diagnosticconcordancebetween The rateofgenetictestingpereligiblepatientyearsurpassed (p respectively (3/2004-9/2013), 12/2009 and 2/2014) (10/2006- 4/2011 vs (5/2010-3/2016) 4/2014 date test (IQR) median EM: or IFM than later chronologically performed were 1.09-1.88; DDEB HR 1.10, 95% CI 0.78-1.56). Genetic analyses to EBS (JEB HR 2.25, 95% CI 1.56-3.25; RDEB HR 1.43, 95% CI greater for JEB and RDEB, and the same for DDEB as compared of undergoing geneticanalysisas afunctionofpatientagewas respectively, on patients with JEB and RDEB versus EBS (76%, 72% vs 44% data available.Geneticanalysiswasmorefrequentlyperformed with patients 760 the in 2018 to 1984 from conducted were tests other. or unknown/unspecified (9%) 79 diagnostic 970 of total A and JEB, (9%) 80 EBS, (27%) 230 DDEB, (15%) 127 RDEB, (40%) 338 of consisting database, the in identified were patients equivocal. were concluded) definitively be discordant, and ambiguous diagnostic tests (e.g. EB type could not were types different concluding tests concordant, were type EB same the concluding tests conclusions: analysis genetic against EBS) DDEB, JEB, RDEB, (e.g. type EB regarding conclusions nostic concordancewasassessedbycomparingEMand/orIFM immunofluorescence mapping (IFM), and genetic analysis. Diag type and diagnostic testing results for electron microscopy (EM), data were retrospectivelyabstractedfromthedatabaseincludingEB Patient analyzed. were 2018 31, December and 2004 1, patients evaluatedat18tertiarymedicalcentersbetweenJanuary & methods:ParticipantsenrolledinalongitudinaldatabaseofEB inform cost-effective management recommendations. and assessthediagnosticconcordanceofthesetestsinorderto the diagnostictestingpatternsinalarge cohortofEBpatients for prognosis, management, and counseling. We set out to define cation of epidermolysis bullosa (EB) have significant implications Introduction & objectives: Accurate diagnosis and subtype specifi in our Hand Therapy Department. To set up the HTO system and within anInformation Technology (IT)governanceframework hand score. To registeraserviceevaluationoftheHTO system outcome measures and automated data analysis, including a total an electronichandtherapypatient recordwithpatient-recorded online (HTO) systemwasdevelopedandvalidated.Itcomprises care andcostsevidencebestpractice. A Hand Therapy- we are unable to chart disease progression, responses to treatment EB. with those for enough specific not also are sures result, a As dressings andcontractures.Currenthandtherapyoutcomemea measurement ofrangemovementiscompromisedbyuse Bullosa (EB) is intermittent, particularly after surgery, and accurate Introduction &objectives:HanddatacollectioninEpidermolysis R .Box ONLINE SYSTEM-INITIAL FINDINGS SERVICE EVALUATION OF A HAND THERAPY P54 to thespecificityafforded bygenetic analysis. diagnosis, they frequently offer equivocal findings when compared workup ofRDEBandJEB. While EMandIFMcancorroborate a in favor of genetic analysis over EM and IFM, particularly in the and 3%, respectively. dant, or discordant in comparison to genetic analysis in 40%, 31%, 1 SUNY Downstate Health Sciences University, Cincinnati Children’s MD, Tor Shwayder, MD, Anne W. Lucky, MD,Sharon A. Glick,MD MD, JohnD.Browning, MD,SusanBayliss,MarlaJahnke, London Guy’s andSt. Thomas’ NHS Foundation Trust, 1 , S.Sooriah p < 0.001). By Cox regression analysis, the likelihood 2 , T. Graham Conclusions: Diagnostic testing has shifted 2 , P. Grocott 2 Results: 2 King’s College Overall 854 Materials < 0.001). - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV information amongsteachother; beingincludedinasupportive multidisciplinary approach, ideally interconnected and exchanging personal assistance; an easy-to-reach support for all needs, using a and financial support as well as every-day support by home care or social psychological, medical, of help the with and training, and possible degree of autonomy, built upon information, knowledge, highest the are: wellbeing psychosocial and life of quality the to a parentofyoungadultwithEB.Results: furthermore them of one support, community and diseases rare in experts them of two therapists), occupational workers, social psychologists, nurses, (doctors, care EB in involved actively them of eight EB, on experts ten interviewed we step, first a As tients’ andtheirfamilies’ viewswillbetakenintoconsideration. experts’where approach, theory grounded a chose pa as well as of peoplewithEBandtheirfamilies.Materials&methods:We research aimstoidentifyfacilitatingfactorsthequalityoflife Our dimensions. functional and emotional, social, physical, into and concerns’’. Health-relatedqualityoflifecanbedivided standards expectations, goals, their to relation in and live they which in systems value and culture the of context the in life, in position their of perception individual’s “the as life of quality (WorldWHO The defines issue. Organisation) important Health for now, there is no cure for EB yet, quality of life is an extremely of rare genetic diseases characterized by skin fragility. As, at least Introduction &objectives:Epidermolysisbullosa(EB)isagroup Sigmund Freud UniversityVienna, FacultyofPsychology Gudrun SalamonandVinzenz Hübl HEALTH CAREPROFESSIONALS AND EXPERTS BULLOSA AND THEIR FAMILIES, IDENTIFIEDBY LIFE OF PEOPLELIVING WITH EPIDERMOLYSIS FACILITATING FACTORS FOR THE QUALITY OF P55 situations impactuponhandtherapy. improved communicationandunderstandingofhowindividual’s and clinicianparticipationindatacapture. The rewardsinclude response totreatmentcareandcosts. The systemreliesonpatient progression, disease charting place, one in captured are data the toring ofpatients’ hand condition between clinic appointments. All been collected.Itisquickandeasytocompleteallowsmoni and contemporaneous qualitative accounts that have previously not and clinician records, with remote capture of objective hand data release. HTO system remotely, including two receiving post-surgical hand the used seven participants, 12 remaining the Of clinic. in lected col were data remotely,their assessments and their complete to IT failure preventingcompletion. Four participantswereunable language). Fifteenbaselineassessmentswereconductedwithone participants were recruited with two exclusions (English not first The system months. was refined10 to meetover service requirements. system HTO the on outcomes own their recorded and monitored assessed, Participants therapists. the by monitoring reciprocal with patients, and therapists hand by mum datacapturetotheHTO systemwasclinicallydetermined Mini 2019). November to (February participate to invited were carers their and intervention, therapy hand undergoing EB, with Toolkit framedtheevaluation. Twenty Englishspeakingpatients National InstituteofHealthResearch Telehealth Implementation HTO systemcomparedwithEPRdataMaterials&methods:The determine theconsistencyandqualityofdatarecordingon Tocarers. and patients clinicians, with system HTO the of bility Patient Records (EPR), over 12 months. To evaluate the accepta hand therapy data with patients, in parallel with current Electronic train participantsindatacollectionandanalysis. To collectroutine Conclusions: The HTO systemfacilitatessharedpatient Facilitating factors Results: Sixteen Sixteen - - - - - age at diagnosis of 30.4 of diagnosis at age cell carcinomaswerediagnosed(5male;2female),withamean patient). During the first period of time (1998-2007), 7 squamous the knees), followed by the cervical region (2 patients) and hand (1 lower limbwasthemostfrequentlocation(7onfeetand4 of 18.6 diagnosis at age mean a with 1female), (6male, diagnosed were the second period of time (2008-2018), 7 epidermoid carcinomas During 85.7%). rate: (mortality disease cancerous the of spread amputation (amputation rate: 71%) and 6 of them died due to the In 2008, we started a new protocol for early diagnosis of epider of diagnosis early for protocol new a started we 2008, In to analyzetheresultsofthisnewprotocol.Materials&methods: bullosa (EB) was started in our Centre 10 years ago; our aim was nosis ofsquamouscellcarcinomainpatientswithepidermolysis Introduction &objectives: An intensiveprotocolforearlydiag Juan CarlosLópez-Gutiérre Muñoz-Serrano,Mercedes Díaz,RocíoMaseda,RaúldeLucas, Carlos Delgado-Miguel, Miriam Miguel-Ferrero, Antonio J. NATIONAL REFERENCECENTRE CARCINOMA: LONG-TERMRESULTS FROM A BULLOSA PATIENTS WITH SQUAMOUSCELL IMPROVING SURVIVAL INEPIDERMOLYSIS P56 3female), with a mean age at diagnosis of 22.4 of diagnosis at age mean a with 3female), Fourteen patientsdevelopedsquamouscellcarcinoma(11male; Results: Fifty-seven patients (28male; 29female) were analyzed. before andafterthenewprotocolwasintroducedwerecompared. lected. The amputation rate and mortality rate of patients treated Demographic data (sex and age) and tumor location were col comparatively. analyzed were protocol) (post-new 2008-2018 carcinoma. Twoand protocol) (pre-new 1998-2007 periods time cell squamous developed who (1998-2018) years 20 last the in treated bytheDepartmentofPaediatricSurgery atourinstitution up visits. We performedaretrospectivestudyinpatientswithEB PET-scan control ofdistancedisseminationandfrequentfollow- suspected of malignancy and early excision of malignant lesions, lesions skin all of biopsies of performance surface, body entire the of exam exhaustive included: which EB in carcinoma moid quality ofliferesearch. psychosocial wellbeingandthusaddsanovelpointofviewto research exploresfacilitatingfactorstothequalityoflifeand Quality oflifeisacentralissueforpeoplelivingwithEB.Our is recommendedinorderto avoid disappointment. to differentiate betweenhopesandexpectations;theiralignment important is it communication, clear and supportive a For time. of the patients’ and families’ expertise and experience, and enough families. Building up such a relation needs honesty, the validation their and patients EB the professionals, care health the between and theirfamiliesarehigherwithastabletrustfulrelation that supportoffers areactuallyacceptedandusedbyEBpatients and theexchangewithotherpatientstheirfamilies.Chances friends, a social surrounding such as and kindergarten, family school, or of work, network personal a of consisting network, social life andlengtheningthesurvival ofpatientswithEB. and treatment of epidermoid carcinoma, increasing the quality of by a trained multidisciplinary team, promotes an earlier diagnosis which relies onthe protocolized study andtreatment ofskin lesions protocol, intensive new this of introduction The Conclusions: statistical significance was observed due to the small sample size. no period, first the of those than lower were rates both Although the mortality rate was 57.1% (OR 0,53 CI95% [0,1-6,1]; [0,1-4,9]; CI95% 0,42 (OR 42.8% was group this in rate amputation The significant. statistically was groups both ± 3.2years. The difference in the age at diagnosis between ± 6.5years. Fivepatientsrequiredlimb Acta DermVenereol Suppl220 Posters ± p 5.5years. The Conclusions: = 0,577) and 0,577) p = 0,512). 0,512). 49 - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Institute, Madrid,Spain ciones Energéticas, Medioambientales yTecnológicas, CIEMAT of anchoring fibrils which form key attachment structures for structures attachment key form which fibrils anchoring of component major the collagen, VII type encoding COL7A1 trauma. RDEB iscaused bya wide variety ofmutations in responsible forblisteringofthe skinandmucosaafterminor sis Bullosa (RDEB) is a rare and severe genetic skin disease Introduction &objectives:RecessiveDystrophicEpidermoly 3 1 Araksya Izmiryan DYSTROPHIC EPIDERMOLYSIS BULLOSA CELLS FROMPATIENTS WITH RECESSIVE PRIMARY AND INDUCEDPLURIPOTENT STEM TWO RECURRENT COL7A1MUTATIONS IN CRISPR/CAS9-MEDIATED CORRECTIONOF P58 a homogeneoustopicalapplicationoftheribopolyplexes. tion, the percentage of stem cells corrected and a formulation for biodistribu the dose, effective minimum the explore and model the confirm to stage this at as a treatment for RDEB. A full preclinical assessment is needed results obtainedindicateaveryhighpotentialoftheribopolyplexes ring type VII collagenexpressiontothepatients’ own cells. The a non-invasivestrategytorestoreintegrityoftheskinbyconfer todevelop seeks proposal paramount.Our potentialis translational clinical significant with strategies treatment of development the therapy beyond palliative care for patients suffering with RDEB, from a biopsy. Conclusion fections weredoneofprimarypatientRDEBkeratinocytecells trans when immunofluorescence by confirmed was restoration VII Collagen RNP. of 8ug with Cat-polymer Y4 by composed ribopolyplexes using when correction 30% achieving exon, the smaller bandcorrespondingtotheshorterCOL7A1onceexcised a obtaining and 80 exon the excising occurred, edition gene the nomic DNA extracted after 72 hours ge of transfection the confirmed that from PCR The biocompatibility. their confirming 70%, over viability cell a induced Cat-Polymers, different by formed complex. After 72 hours post-transfection all the ribopolyplexes, the to added (red) tracrRNA the of fluorescence by transfection Results: keratinocytes, by alamarBlue test, PCR and immunofluorescence. molysis bullosa(RDEB)keratinocytelineandprimaryRDEB post-transfection inanimmortalizedrecessivedystrophicepider and efficiency of the ribopolyplexes was evaluated after 72 hours in vivoforRDEB.Materials&methods:Thebiocompatibility plexes asatherapeuticmoleculetorestoreCOL7A1expression ribopoly our of efficiency the test to was work this of objective developed to be a topical treatment for RDEB. Therefore, the main common mutation sites, this medical unit (ribopolyplex) has been COL7A1 gene by excision of the mutated exon 80, one of the most (RNP), forming a medical unit to treat RDEB editing the mutated signed tobecomplexedwithCRISPRribonucleoproteincomplex de specifically (Cat-Polymers) polymers cationic hydrophobic Introduction &objectives:Recentlywehavedevelopednew Irene Lara-Sáez NANOPARTICLE TO TREATRDEB RIBOPOLYPLEX: THE GENEEDITING P57 50 1 Wang Marta García land, APHP, Paris,France UMR 1163, Paris,France; Charles Institute of Dermatology, UniversityCollege Dublin, Ire- Department of Genetics, Necker Hospital for Sick Children, Imagine Institute, Laboratoryofgenetic skin diseases,INSERM 1 2 Universidad CarlosIIIdeMadrid,Spain, EB2020 1 Intracellular localisationwasobserved72hoursafter 2 , RodolfoMurillas 1 , Jonathan O’Keeffe-Ahern 1,2 st WorldCongressonEpidermolysisBullosa , CamilleBerthault : Given that currently there is no clinical efficiency in a murine RDEB murine a in efficiency in vivo 2 University ofParis,France, 3 , FernandoLarcher 1,2 , Alain Hovnanian , Alain 1 , Sigen A , 3 Centro Investiga 1 , QianXu 3 , Wenxin 1,2,3

1 ------, skin modelssuitableforclinicalapplication. recurrent RDEBmutationsforthedevelopmentoftransplantable precise genomeeditingisanewandpromisingstrategytocorrect Therefore, iPSCs. and cells patients’primary in HDR mediated COL7A1 repairoftwofrequentmutationsthroughCRISPR/Cas9- populations. dilutions andpropagationtobypasscellularheterogeneityinbulk gene-corrected primaryRDEBkeratinocytesandiPSCsbyclonal as assessed by Western blot analysis. Currently, we are enriching and confirmed type VII collagen re-expressionfibroblasts at theand protein level, keratinocytes into re-differentiated were which iPSCs, RDEB in observed was correction 20% to Up analysis. blot western by confirmed was re-expression Typecollagen VII bulk-nucleofected primary RDEB cells, as assessed by RT-qPCR. tion. GeneticcorrectionofCOL7A1wasestimatedtobe10%in with thecorrespondingDonordeliveredasssODNbynucleofec together RNPs site-specific with iPSCs and cells RDEB primary treated we purpose, correction gene For sites. predicted in-silico the at activity cleavage non-specific for evidence no found and off-target activity in primary RDEB keratinocytes and fibroblasts, ribonucleoprotein complex(RNP). We havealsoevaluatedtheir a as Cas9 with together delivered when iPSCs, and fibroblasts keratinocytes, RDEB in activity cleavage 70% to up showed gRNAs these Twoof 80. exon in and 3 exon in corrected be to mutation the to distance close in sequences or mutation specific the targeting (gRNAs) RNAs guide different designed we First, the CRISPR/Cas9 system in primary RBEB cells and in iPSCs. of delivery non-viral through correction COL7A1 efficient ved fibroblasts. RDEB from derived iPSCs while thesecondapproachisbasedoncorrectionofRDEB on the correction of RDEB primary keratinocytes and fibroblasts, based is approach first The parallel. in developed are strategies 80, respectively. or the c.6508C>T (p.Gln2170*) mutations in exon 3 and in exon (p.Lys142Arg)These cellsarehomozygousforthec.425A>G mutations inRDEBpatient’s primary and iPSCs-derived cells. logy DirectedRepair(HDR)tocorrecttworecurrentCOL7A1 mutations werefoundinthepanel ofEBSgenesavailableatthat ferences between patient and control in keratin 14 staining but no investigations. Skin immunofluorescence revealed significant dif autoimmune blisteringskindisease wereexcludedbyappropriate and dermatosis plantar juvenile , pompholyx tinea, of diagnoses sites ofrecentblistersbutnoactive blistering. The differential at hyper-pigmentation and feet damp spaces, toe-web the of maceration toenails, fifth thickened revealed years 11 age at Examination history. family relevant no with unaffected, were siblings 3 her and consanguineous, were who parents, Her well. physical educationactivitiesmostofthetime.Shewasotherwise she was able to tolerate sandals and flip flops and to participate in curred only in hot weather and was worse with friction, although associated withgradualthickeningoftoenails. The blisteringoc age, of years 8 about from feet, the to confined blistering, itchy EBS caused by DST mutations. Our patient suffered recurrent of type recessive autosomal rare a with patient a in findings the new variantsmakeaccuratediagnosischallenging. We describe emergence of the and factors phenotype. These non-specific and mild relatively a with often EB, of subtype heterogeneous most Results: 2 M. Ogboli AUTOSOMAL RECESSIVEEBSB2 NOVEL MUTATION INDST GENECAUSING P59 1 therapeutic potentialofexvivoCRISPR/Cas9-mediatedHomo dermal-epidermal adhesion. Ourstudy aims at investigating the Genetics department,BirminghamWomen’s Hospital Deparment ofDermatology, BirminghamChildren’s Hospital, Epidermolysis BullosaSimplex(EBS)isgeneticallythe 1 , D.Walsh In our study,our for In evidence Conclusions: provide we Materials &methods:To achieve this goal, two 2 , G.Ryan 2 , C.Moss Results: 1 Here, we achie we Here, - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV of gastrostomyplacementforRDEB-GS patients. and co-centrestudieswillprovide furtherinsightintotheimpact time iftheydidnothaveagastrostomy placed.Furtherlongitudinal GS patientsshowedanoverallloss ofweight-for-age zscoreover regardless oftheir age orthe age ofgastrostomy insertion. RDEB- a gastrostomy was placed, or if a gastrostomy was already in situ, showed asubstantialimprovementinweight-for-age zscoreonce tial significant faltering growth. received intensivedieteticinputandhadnotyetdisplayedpoten had therefore, completion), at months (40,62,83 cohort total the weight-for-age zscore.3ofthese4patientsweretheyoungest SD). Only 4 of these 11 (36%) patients had an individual gain of overall weight-for-age z score loss of -0.32 SD (range -1.72 – -2.2 patients didnothaveagastrostomyplacedandhadanaverage average increase of +0.62 SD (range 0.23-1.09SD). 11/19 (58%) (100%) had an overall increase in weight-for-age z score with an 4/4 107months). (mean months 76-146 from ranged insertion of had agastrostomyplacedduringthedatacollectionperiod. Age average gain of +0.66 SD (range 0.34-1.09). 4/19 (21%) patients these patients hadanoverallincreaseinweight-for-age zscorewithan of (100%) 4/4 period. collection data the to prior placed rostomies placed. 4/19 (21%) patients already had a gastrostomy data was analysed. 10/19 (52%) were male. 8/19 (42%) had gast recorded. age, date of gastrostomy insertion and weight-for-age z score was height, weight, 2013-2019; between consultation patient each at collected was Data ofthepaediatricEBservice. patients and were a gastrostomy. Materials&methods: All patientshadRDEB-GS by comparingweight-for-age zscoresofpatientswithandwithout a cohort of paediatric patients with RDEB-GS at a national centre, will analyse the impact of gastrostomy placement on weight gain in ment hasongrowthinRDEB-GSpatients. This retrospective study evidence exists demonstrating the impact that gastrostomy place challenging duetoconcernsofpossiblecomplications.Minimal placement is considered early on. Families often find this decision growth-faltering. In anticipation of growth-faltering, gastrostomy these highrequirementsthroughoraldietalonewhichleadsto tritional demands of RDEB-GS commonly outweigh achieving nu The malabsorption. and infection healing, wound as such elevated nutritionalrequirementsduetoacombinationoffactors epidermolysis bullosageneralisedsevere(RDEB-GS)encounter Introduction &objectives:Patientswithrecessivedystrophic Great OrmondStreet Hospital,London. Natalie Yerlett, DrGPetrof, MrJCurryandDr A EMartinez. GENERALISED SEVERE DYSTROPHIC EPIDERMOLYSIS BULLOSA- IN PAEDIATRIC PATIENTS WITH RECESSIVE PLACEMENT ON WEIGHT-FOR-AGE ZSCORES ESTABLISHING THE IMPACT OF GASTROSTOMY P60 the EB phenotype seen here is characteristic of exon 23 mutations. that and pathogenic, is patient our in found variant DST zygous J Invest Derm 2017;137:2227-2230). We conclude that the homo widespread, somewhat pemphigoid-like blistering (Turcan I et al. a prominentfeatureofpatientwithexon24mutationsandmore disease including neuropathy. Pruritis, as seen in our patient, was widespread more cause can elsewhere mutations but 23, exon in a similarlocalizedEBSphenotypeandbiallelicDST mutations andmuscle. system Two familieshavebeenreportedwith previous letal filament networks. DST is expressed in skin, central nervous a memberoftheplakinfamilyproteinswhichbridgecytoske truncated protein. DST encodes dystonin, also known as BPAG1, DST,p.(Asn1823LysfsTer9)of c.5469_5470del, 23 a predicting sequencing showedanovelhomozygousframeshiftvariantinexon genome Whole project. genome 100,000 UK the into recruited therefore was She and TGM5. 14 keratin 5, keratin namely time Results: 19 patientsmettheinclusioncriteriaandtheir Conclusions: RDEB-GSpatients ------James compared using z-scores, children aged 10-15 years were com were years 10-15 aged children z-scores, using compared were changes years’weight 0-10 aged Children changes. height insertion were analysed. Z-scores were calculated to compare Weight and height measurements at insertion and 12 months post collectedfromelectronicandpaperhealthrecords. procedure were operative and insertion at age gastrostomy, for reason subtype, EB Demographics, 2003-2019. between insertion gastrostomy underwent who EB, with children 32 of study observational tive in ourcohort.Materials&methods:We conductedaretrospec favoured. We reviewed the early effects ofgastrostomy placement status1. The laparoscopically-assistedtechniqueisincreasingly been showntobeeffective inimprovingEBpatients’ nutritional EB childrenduetomucosaltrauma.Gastrostomyfeedinghas tube feedingisnotalong-termoptionfornutritionalsupport including reducedoralintakeandmucosalfragility. Nasogastric with epidermolysisbullosa(EB)addressesmultiplechallenges Introduction &objectives:Nutritionalmanagementofchildren A.Z. Mughal CHILDREN WITH EPIDERMOLYSIS BULLOSA FOLLOWING GASTROSTOMY TUBE FEEDINGIN A RETROSPECTIVEREVIEW OF GROWTH P61 Introduction &objectives: Transition ofcareforpediatric pa Phoenix Children’s Hospital,USA per N.PriceMD Judith O’HaverPhD,RN,CPNP-PC, Kellie Badger BS,RN,Har EPIDERMOLYSIS BULLOSA TRANSITION CAREFOR ADOLESCENTS WITH P62 of Effectiveness (2018). K. Carvalho, and L. Castro, E., Dutra, A., Zidorio, 1. Reference gastrostomy tubefeedinginchildrenwithEB. up as the children grow older will show long-term implications of related mortality in the first 12 months post-gastrostomy. Follow- review has shown improvements in height and weight with no This patients. of cohort our in confirmed been has this and EB feeding canassistinthenutritionalmanagementofchildrenwith -0.01). to -4.04 (range -1.78 to -0.13) to -4.51 (range -2.83 from: increased z-scores BMI age mean of years 10 over patients in 1.42); to -3.99 (range -1.80 to mean weight z-scores improved from -2.59 (range -4.36 to 0.54) years, 0-10 aged patients In 0.34). to -4.26 (range -1.77 to 0.45) was observed 12 months after gastrostomy: -2.04 (range -5.26 to and one unableto stand). An improvement in mean height z-scores months, one device removal, one relocation, one unrelated death for 24/32 (four patients excluded due to insertion within last 12 data height and patients, 25/32 for available was post-insertion 9.4%). Weight(3/32, strictures oesophageal rent months 12 data recur and 9.4%) (3/32, dysphagia 6.3%), (2/32, swallow unsafe were insertedduetofalteringgrowth; other indicationsincluded laparoscopic gastrostomy. The majority of gastrostomy tubes was 7.05 years (range 1.0-15.2). 27/32 (84.4%) patients underwent junctional EBand1Kindlersyndrome.Medianageatinsertion lex, 1 EB simplex with muscular dystrophy, 2 generalised severe 27 severe recessive dystrophic EB, 1 generalised severe EB simp included: were data complete with male) 20 female, (12 patients during puberty).Results: pared using BMI z-scores (preferred due to variable weight gain ham Children’s Hospital ham Children’s Hospital, 1 Children’sHospital, University of Birmingham, 179(1), pp.42-49. Dermatology, of Journal British review. systematic a bullosa: epidermolysis gastrostomy forimprovingnutritionalstatusandqualityoflifeinpatientswith 2 , G.Soccorso 1 , S.Unter 4 4 , M.Ogboli Department ofPaediatricSurgery, Birming- 2 , R.Jones 35 patientshadagastrostomy. Only 32 3 Department ofDietetics, Birmingham 2 Deparment ofDermatology, Birming- 2 Conclusions: Gastrostomytube 3 , M-L.Lovgren², J.Heaton Acta DermVenereol Suppl220 Posters 2 , D. 51 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Hospital, London. preoperatively andtoobservetheir recurrencepost-handsurgery. adduction thumb and flexion finger (pseudosyndactyly), spaces hand Contractures in Epidermolysis Bullosa (AChE), to score web formal jointreleasewasperformed. We usedour Assessment of but usually required fishmouth release atpossible, PIP +/- DIPwhere joint levels. No dermis the of thickness full the breaching without released were fingers the graft, push a and Matriderm the patient and family. The 1st web was released and covered with was performedafterMDT discussionsandseveralmeetingswith including survivorshipofsurgery. Materials&methods:Surgery the impactonhandofsurgical interventionforcontractures of thewholehandtoestablishchange.Ourpurposewasassess function butlimitedassessmentsthatassessabnormalanatomy offunction. loss ofpaediatrichandThere aremanymeasures despite limited anatomy, and to have improved appearance, despite troublesome. Patients have the ability to maintain some function, ongoingandprogressivehandcontractureis with vention inRDEB Introduction &objectives: theoutcomeofsurgicalAssessing inter Plastic Surgery Gill Smith CONTRACTURE PAEDIATRIC EPIDERMOLYSIS BULLOSA HAND ASSESSING THE OUTCOMEOF SURGERY FOR P63 and lessonslearned. barriers, program, the of aspects key highlighting presented, be being tested in this population. Results from this ongoing pilot will the guidelinesfromGot Transition programandcurrently is chronic disease is sparse. A pilot program was developed using literature fortransitionofadolescentdermatologypatientswith cent patientdiagnosedwithEBtoanadultcenteredmodel. The of careprogrampublishedonamethodtotransitiontheadoles intheorganization.populations Conclusions: nostandard There is Results willbeusedtomodelthiscareplanforotherapplicable this. address to process a as well as identified being are care to use withapilotgrouptoensureconsistencyindelivery. Barriers Eligible patients were identified and a protocol was developed to documentation wasincorporatedintheelectronichealthrecord. this population. A policystatementwasdevelopedandasectionfor Got Transition model to formulate an innovative pilot program for multidisciplinary teamadaptedtheserecommendations using the children with severe EB at Great Ormond Street Hospital. Our for program transition the described that (2007) Holmes and the EnglishlanguageliteratureyieldedasinglearticlebyFoster Health. Advance Adolescent Maternal and Child Health Bureau and The National Alliance to conditions. This programisacooperativeagreementbetweenthe chronic from apediatrictoadultmodelforchildrendiagnosedwith the institutionhasselectedthisprocesstoguidetransitioningcare Transition programwasselectedforthisEBtransitionalcareas care foradolescentsdiagnosedwithEBwasperformed. The Got methods: adult centeredcareinpatientsdiagnosedwithEB.Materials& to describe a pilot program for the transition ofadolescent to tidisciplinary team/center. The purposeofthispresentationis dermatologist thatseesbothadultsandchildrenand/oramul a dermatologist, pediatric a by locally for cared be may patients patients withepidermolysisbullosa(EB)arenodifferent. These rare diseases often remain in the care of their pediatric team; lenging forpatientswithrarediseases.Manyadult caring foradultstobeapartofthetransitionteamisoftenchal life-limiting diagnosesarelivinglonger. Identifyingphysicians countries. As medical therapies advance, patients with previously developed in topic” “hot current a is diseases chronic with tients 52 EB2020 1 A reviewofthecurrentliteratureregardingtransitional 1 , NickyJessop 1 andOccupational Therapy st WorldCongressonEpidermolysisBullosa 2 andCatherineMiller Results: A comprehensivereviewof 2 , Great OrmondStreet 2 - - - - W. Bauer Gruber Austria, versity Hospital oftheParacelsusMedical University Salzburg, Reichl vestigate the individual and combined effects ofthe substances. In APOSSIBLE TARGET EPIDERMOLYSIS BULLOSA:MITOCHONDRIA AS CELL CARCINOMA INPATIENTS WITH TREATMENT OF AGGRESSIVE SQUAMOUS P64 decisions abouthandsurgery. surgery. We hopetohelpcliniciansandfamilies make informed of survivorshiptheindividualcomponentsreleaseafter be combined with a functional measure. It allows an assessment surgery using AChE. There wasashortsurvivorship. This should able toassessrecurrenceandprogressionofcontracturesafter of thecontracturewithfunctionpreserved.Conclusions:We were metimes thisrepresentedaworseningofdifferent component returned totheiroriginaltotalscoreby2yearspostsurgery –so quickly than 1st web space adduction contracture. Most had more recurred deformity flexion Finger increased. scores their and function lost they recurrence, with as, time with decreased both appearanceandfunctionaftersurgery butthisgradually (median 24months).Results: Individual handswerefollowedupforamaximumof53months month priortosurgery andrepeatedonroutinetherapyreview. the thirdepisodeofsurgery. The AChE wasperformedwithinthe had repeatsurgery on4hands–foronepatientand2itwas One hadprevioussurgery tooneelsewhere. Three patients dures, operated on by the same surgeon, at a mean age of 7 years. In vitrostudiesincludedclonogenicity -andMTT-assays toin the growthofhumanandmurine SCCbothinvitro andinvivo. against KD and doxycycline cetuximab, metformin, of use the tumor metabolism. Materials & methods: Here weinvestigate to identifynoveltreatmentoptions forRDEB-SCCbytargeting purpose istoreduceskintoxicitiesofestablishedtreatmentsand KD can be a promisingstrategyfor adjuvant cancer therapy. Our cancer cells.Combiningmetabolicallyactivecompoundswith a to standardtreatmentbyutilizingthereprogramedmetabolismof fat, low-carbohydrate ratio, appears to sensitize most cancer types in vivo. Additionally,high- a has which (KD), diet ketogenic the mitochondrial activityandexertanti-neoplasticeffects invitro and promising target. Metforminanddoxycyclinebothcompromise a be to appears this biogenesis, mitochondrial on depend cells alternative treatmentoptionsareneeded. As manytumorstem and combinatorial Therefore, group. patient this in limiting be can toxicities skin dose-dependent its however, RDEB-SCC, RDEB-SCC. Cetuximabwassuccessfullyappliedformetastatic metastatic only treatmentoptionsfor chemotherapy constitutethe mortality.premature of cause primary Surgery, and radiotherapy the constitutes which (RDEB-SCC), carcinomas cell squamous bullosa (RDEB) patients are at high risk for developing aggressive Introduction &objectives:Recessivedystrophicepidermolysis 1 Tobias Welponer cal UniversitySalzburg, Austria, We report the results for 7 patients, 10 hands and 14 surgical proce deh Aminzadeh-Gohari burg, Austria, *equalcontributors University HospitaloftheParacelsusMedicalSalz- Biochemistry andTumorMetabolism, DepartmentofPediatrics, burg, Austria, Medical UniversitySalz- University HospitaloftheParacelsus Genodermatoses, DepartmentofDermatologyand Allergology, EB House Austria, Research Program forMolecularTherapyof 1 , Anna Kaufmann , Anna 1 *, JosefinaPiñónHofbauer 3 1,2 Department ofLaboratoryMedicine, ParacelsusMedi- , Julia Reichelt 2 Department ofDermatologyand Allergology, Uni- 1,2 , LisaTrattner 4 , Réné Feichtinger 1 , MelanieKienzl 1 , Barbara Kofler Patients wereinitiallyhappywith 4 Research Programfor Receptor 1 * 1 , Birgit Tockner 1 4 , Thomas Felder , Thomas , Roland Lang 4 , ChristinaGuttmann- 1 , Victoria 2 , Johann 3 , Sepi- - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV dakshira, MD noi, MD,DNB 49 patients/parents gave consent for biopsy, which was evaluated had DDEB, and 2 patients had Kindler syndrome. Of 60 patients, patients Eight type. intermediate generalized RDEB had 10 and type ofJEB.Fifteenpatientshad RDEBgeneralizedseveretype generalized intermediate, and 9 patients had a generalized severe JEB had patients Five EBS. type severe generalized had 2 EBS, EBS- localized type, 2 patients had generalized intermediate had type patients 7 CDM, on based patients, 60 the Of criteria. sion and includedinthestudyaftersatisfyinginclusionexclu Results: lysis wasdoneusingtargeted next-generationsequencing(NGS). ana mutational possible, literature. Where-ever the in described of blistering or tissue splitting to be ascertained as per the features blocks andultramicrotomy. Semithinsectionsenabledthelevel for lightmicroscopy. This wasfollowedbythetrimmingofresin sections thick) mm (0.5–1.0 semithin informative of provision dehyde. The samples were divided to allow adequate fixation and glutaral containing fixative TEM the in immersed immediately VII, collagen XVII, and collagen IV. For TEM, the samples were used for the IFM were against cytokeratin 14, laminin 5, collagen skin biopsy was taken for TEM and IFM. The primary antibodies clinical diagnosis of EB. After a complete physical examination, a observational studyincludedallpatients(aged limited numberofpatients.Materials&methods:Thisprospective (TEM) in the diagnosis of EB, and with mutational screening microscopy in a electron transmission and (IFM), mapping antigen to correlate the performance of CDM versus immunofluorescence with themoleculardiagnosis. The primaryaim ofourstudywas dermolysis bullosa(EB)whichshowedahighconcordancerate (CDM) was developed and validated forthe diagnosis ofepi IntroductionRecently, &objectives: matrix diagnostic clinical a 2 1 Rahul Mahajan,MD BULLOSA SEQUENCING INDIAGNOSINGEPIDERMOLYSIS MICROSCOPY AND NEXT GENERATION ELECTRON MAPPING, TRANSMISSION MATRIX,IMMUNOFLOURESCENCE ANTIGEN CORRELATION AMONG CLINICAL DIAGNOSTIC P65 efficacy ofthisstrategyagainstRDEB-SCC. metformin anddoxycyclinearewarrantedinordertoevaluatethe be reduced. Further investigations into pathways impacted by and consecutivelyskintoxicitiesofcetuximabcouldpotentially dosage cetuximab, with doxycycline or metformin combining pathogenic skininfectionslinkedtotumordevelopment.By controlling in benefits additional pose may Doxycycline effects. tumor cells, the combination of both drugs could induce additive metformin anddoxycyclineimpedemitochondrialbiogenesisin both serum levelsintype-2-diabetespatients.Conclusions: As concentrations ofmetformininthemicewerebelowtherapeutic mice. serum the sacrifice, effectson At adverse no with survival overall in increase significant statistically but small a in resulted alone metformin However, burden. tumor reduce not could min lations administered ad libitum and also combined with metfor human RDEB-SCC lines in vitro demonstrated significant anti-proliferative effects against several Metformin, cetuximab, and doxycycline, alone or in combination and treatedthemwithKDand/ormetforminadlibitum.Results: our Bishan DassRadotra,MD Education andResearch, Chandigarh, India Department of Histopathology, Postgraduate Institute of Medical Department of Dermatology, Venereology, and Leprology, and in vivomodelweinjectedmurineSCC VII cellsinC3Hmice Sixty patients with EB, diagnosed clinically were screened 2 1 , Debajyoti Chatterjee, MD,DM , DipankarDe,MD 1 , SeemaManjunathMD, 2

. In our in vivo 1 , Sanjeev Handa, MD,FRCP 1 > , ManojGopalMa- model KDformu 6 months) with the 6 months)withthe 2 , Anuradha Bish- , Anuradha 1 ------, Peñarrubia Hospital SantJoandeDéu(Barcelona) 1 and theleastbetweenCDMIFM. IFM, and TEM by followed TEM and CDM between seen was 88.9% (8/9), respectively. and (7/9), 77.8% (9/9), 100% at estimated were IFM and TEM CDM, of sensitivity the EB, diagnosing for standard gold the as Although doneforasmallnumberofpatients(n social rejection, constipation, sleep problems and school integra dysphagia, infections, psychological problems, economic impact, parents indicated the following EB-related problems: pain, itching, the concern, of order descending In cases. of 75% in 5 was unit answered byatotalof4parents. The overallsatisfactionwiththe and 51interdisciplinary case discussions. The questionnaires were follow-ups 319 visits, first 2 were hospital. There the in 100 and to-face services, of which: 40 were at home or in the community EB, a total of 159 calls have been made, 39 by email and 140 face- with atotalof15patientsregisteredintheunitsometype included bothparents.Results: of concernabouteachEB-relatedproblem. The studypopulation scale 1-5onthedegreeofperceivedsatisfactionand ad-hoc questionnairewithopenquestionsandscoringonaLikert tool forcollectingdataonfamilieswasacorporativemailingofan in themedicalhistoryandunit’s computerizeddatabase. The SATISFACTION PATIENT UNIT AND FAMILIES’ PERCEIVED UP BY A PEDIATRIC COMPLEXCHRONIC SEVERE EPIDERMOLYSIS BULLOSA:FOLLOW- P66 (k TEM and CDM between subtypes (p ficant difference in all IFM findings studied among the major EB 3 patients, IFM findings were not confirmatory. There was a signi (40.8%), DEB in 18(36.7%) and kindler syndrome in 2 (4.1%). In findings, a diagnosis of EBS was offered in 6 (12.2%), JEB in 20 anchoring fibrils; of preservation vacuolations, cell basal plates, dense sub-basal pes (Tonofilaments clumping, characteristics of hemidesmosomes/ electron microscopy findings studied among all the major EB in subty difference significant a was There 1(3.3%). in syndrome Kindler and (53.3%) 16 in DEB (20%), 6 in JEB (23.3%), 7 in 30 samples evaluated with TEM, a diagnosis of EBS was offered be evaluatedformutationalanalysisusingtargeted NGS.Outof could patients 9 Only IFM). 49 and TEM (30 microscopy cence and supportintheinitialstagesof thediseaseaspositivepointsof tion, among others. Families highlight nurses’ care, 24-hour care (n diagnosis registered in the UCCP on September 2019, aged 0-18 Descriptive observationalstudycarriedouttopatientswithanEB and satisfactionwiththefollow-upoffered. Material&methods: to know the families’ perception regarding their main concerns type ofinterventionsperformedinoneyearwiththesepatientsand the describe to are: objectives main community.The and home hospital, in in-person and telematically 24-h offered is care The a multidisciplinary team that offers patient & family centered care. tient care (UCCP) was started to respond to this kind of patients, as bullosa (EB). In 2012, a specialized unit for complex chronic pa Within this definition we found patients with severe epidermolysis fragility, with multiple bio-psycho-socio-spirituals related needs. with alimitingand/orlife-threateningconditionthatimplieshigh one is disease chronic complex AIntroduction andobjectives: Inés Cases using transmission electron microscopy and/ or immunofluores or and/ microscopy electron transmission using (k Pediatric ComplexChronic Patient Unit, = = 15). The datawascollectedfromtheinformationrecorded 0.8, p = 1 1 , Silvia Ricart < , MartaViñals 0.0001), and TEM and IFM (k IFM and TEM and 0.0001), 0.0001). There was statistically significant agreement p < 0.0001). Of 49 biopsies evaluated with IFM 1 , Eduard Pellicer 1 Conclusions: The highestconcordance , IsabelTorrús = 0.931, From January to September 2019, Acta DermVenereol Suppl220 p = 0.0001), CDM and IFM and CDM 0.0001), 1 , Asunción Vicente, Asunción 1 2 , Silvia Ciprés Dermatology Service, = 0.883, = Posters 9), taking NGS p = 0.0001). 1 , Lucía 2 53 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Peñarrubia Sant JoandeDéuHospital(Barcelona) 1 M. D.Malta EPIDERMOLYSISBULLOSA VARIANTS SIGNATUREDYSTROPHIC AMONG EXTRACELLULAR MATRIX DISTINCT P68 to quantifyitseffectiveness throughoptimaltools. terventions moreareplannedinpatient’s schoolanditisplanned in 4 least at course, 2019/2020 the During topic. the in interest consider thatthistypeofinterventionraiseawarenessandarouse the educational community. Given the student’s participation, we empowered has and patient the for beneficial been has perience been designedforschoolsofchildrenlivingwithEBandtheex (September 2019). relationship withhispartnersatthebeginningofnextcourse patient andhisfamilyreportedsubsequentwell-beinggood the Subjectively, head. center’s the by received was response no responsefromteacherstothesatisfactionsurvey. Subjective a total of 10 questions that were answered by the nurse. There was 100% answers to the student’s pre-test. After the session, they sent for teachers.Results:Assistanceof43studentsand10 Evaluation: ad-hoc pre-test for students, ad-hoc satisfaction survey generate questionsthatwillbeansweredbythenurselater-. 3. will which – debate and workshop session, interactive activity: delivery ofdocumentationandcontacttheUnit.2.Students’ social worker. It consists in 1. Teachers’ activity: training session, their students, carried out in June 2019 by a nurse, psychologist and emotional involvement; The interventionisaimedatteachersand of an 11-year-old boy with recessive dystrophic EB, with marked designed tocarryouteducationalinterventionintheclassroom that contributetoisolation.Matherials&methods: A pilot test is in educational communityaboutthediseaseanddenyfalsebeliefs awareness Raise 3) and children, these of handling safe the for teachers Empower 2) environment, usual their in integration whose mainobjectivesare;1)Improvechild’s qualityoflifeand EB, with living children of schools in intervention psychosocial with schools.Itisproposedtheimplementationofahealthand hospital thereisaneed to standardize the interventionperformed From theChronic-Complex-PatientUnitofathird-levelpediatric indicated. their inclusion and avoid referral to specific center when it is not promote schooling, safe ensure to essential is educators to ledge for childrenwithepidermolysisbullosa(EB)andprovidingknow maximize schoolchildren’s capacities.Providingpropersupport of theperson.Itmustadaptandrespondtoindividualneeds development social the for essential development, physical and Introduction andobjectives: Schooling is a key phase in emotional Inés Cases IN SCHOOL:EPIDERMOLYSIS BULLOSA SINCERELY SPEAKING ABOUT A RAREDISEASE P67 improve thepatientsandfamilies’ qualityoflife. to continueimprovingthedailypracticeofprofessionalsand to knowwhataspectsconcernthecaregiversofchildrenwithEB model hasshowntobewellappreciatedbyfamilies.Itisimportant greater home care. Discussion the follow-up;theyalsoindicatethatwouldpositivelyvalue 54 1 A. F. Carvalho Barco, Guimarães, Portugal, and Regenerative Medicine AvePark, ZonaIndustrial daGandra, ters oftheEuropean Instituteof Excellence on Tissue Engineering Biodegradables and Biomimetics, University of Minho, Headquar 3B’s Research Group, I3Bs–Research Institute on Biomaterials, Pediatric ComplexChronic Patient Unit, EB2020 1 1 1, , Silvia Ricart MartaViñals 1,2,3 1,2 , H.Osório , M.T. Cerqueira st WorldCongressonEpidermolysisBullosa Conclusions: An educationalinterventionhas 1 , Eduard Pellicer 1 , IsabelTorrús 4,5,6 , C.Guttmann-Gruber : The patient & family centered care 2 ICVS/3B’s–PTGovernment Asso- 1,2 , A. P. Marques 1 , Asunción Vicente, Asunción 1 2 , Silvia Ciprés Dermatology Service, 1,2,3 7 , T. Kocher 1 , Lucía 2 7 - - - - , Porto, Portugal, ciate Laboratory, Braga/Guimarães,Portugal, cm per cells 50x103 of density a at seeded were cells RDEB). The DDEB, generalized intermediate RDEB and generalized severe and immortalizedcelllinesofthreeDEBvariants(generalized of the disease. Materials & methods: Healthy primary fibroblasts variants representative between as well as individuals, healthy differences inECMcomposition betweenDEBpatientsand initially anticipated. Hence, this work aims to unravel the main of biologicandclinicalphenotypesDEBtobewiderthan spectrum the found studies several Moreover, scarce. still is microenvironment, particularly on extracellular matrix (ECM), the consequences of different COL7A1 mutations in the cell regarding information However, inheritance. recessive and rent clinical variants have been described with both dominant bullosa(DEB).Diffeall formsofdystrophicepidermolysis cause junction, dermal-epidermal the in fibrils anchoring the of component major the protein, VII collagen encodes which gene, COL7A1 the in Mutations Introduction & objectives: C. O’Connor PHENOTYPE RARE EPIDERMOLYSIS BULLOSA GENOTYPE- MUTATIONS INCOL7A1:CASEREPORT OF A ASSOCIATED WITH RECESSIVEHOMOZYGOUS EPIDERMOLYSIS BULLOSA PRURIGINOSA P69 Medicine (H2020-WIDESPREAD-2014-1-739572). Union for The DiscoveriesCentreforRegenerativeandPrecision European the (ERC-2016-COG-726061) ECM_INK – Grant contract CEECIND/00695/2017 (MTC), the ERC Consolidator and (MDM) SFRH/BD/137766/2018 grant for FCT nowledge features. the generation of further knowledge on DEB variants molecular to contributes work our Overall, proteins. structural ECM the mostly affecting microenvironment, cell impacts collagen VII tionally, our results also demonstrated that a partial loss of type VII hasanenormousimpactondermalECMdynamics. Addi corroborate previousstudiesshowingthattotallossofcollagen observed. was 2, and 1 loproteinases metal matrix and V and III I, collagens namely remodelling, a down-regulationofproteinslinkedtoECMstructureand disease, of severity increased to associated phenotypes the For were foundtobedifferently expressed betweenDEBvariants. homolog 2. Furthermore, ECM organization-associated proteins players such as collagen XII, decorin, biglycan and lysyl oxidase ECM organization throughthedown-regulation ofmajorECM – the different COL7A1mutations studied impacted dermal of theDEBvariant – anditsassociatedclinicalaggressiveness DEB variant have their ownproteomic signature. Independently of the extracellular proteome revealed that fibroblasts from each gical pathways linked to the obtained results. used to confirm the proteomic results and investigate the biolo blot, quantitative real-time PCR and histological methods were by the different cell populations. Then a combination of western quantification was used to assess changes in the ECM deposited maximum ECMdeposition.Massspectrometry-basedlabel-free gal, e ImunologiaMoleculardaUniversidadedoPorto,Portu- dade doPorto,Portugal, 4i3S -InstitutodeInvestigaçãoeInovaçãoemSaúde,Universi at University of Minho, Avepark, Barco, Guimarães,Portugal, Centre forRegenerative and Precision Medicine, Headquarters University,Salzburg, Austria and Allergology, University Hospital of the Paracelsus Medical lecular Therapy ofGenodermatoses,DepartmentDermatology 2 for 14 days with 50μg/mL ascorbic acid, in order to promote 6 FMUP – Faculdade de Medicina da Universidade do Porto, : The authors would like to ack to like would authors The Acknowledgements: 1,2 , S.O’Shea 7 EB House Austria, Research Program forMo- 2 , J.McGrath 5 Ipatimup -InstitutodePatologia 3 Conclusions: Ourresults , J.Bourke Results: 3 The Discoveries 1,2 Analysis - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV pital, London tional Diagnostic Epidermolysis Bullosa Laboratory, Guy’s Hos- 1 South Infirmary Victoria University Hospital, Cork, Ireland, Cork, Infirmary Hospital, South University Victoria terno InfantildelaProvincia deSalta, Argentina extremities andthetrunkis oftenaccompaniedbyfocalpal Hyper- andhypopigmentationofthe skin beginsinchildhoodthe and it is clinically indistinguishable from EBS severe generalized. birth, at present are erosions and Blisters bullosa. epidermolysis form rare a is 131960) OMIM (EBS-MP pigmentation mottled Introduction &objectives: Epidermolysisbullosa simplex with M. Natale MOTTLED PIGMENTATION EPIDERMOLYSIS BULLOSA SIMPLEX WITH PATHOGENIC VARIANT ASSOCIATED WITH HIGH PREVALENCE OF AN INFREQUENT P70 more consistentwitharecessivemechanismofpathogenicity. or toenail dystrophy in the patient’s parents and four siblings is EB by itself. However, the lack of clinical features of skin fragility interference. Thus each mutation could cause dominant dystrophic skipping. Suchexonskippingcouldleadtodominant-negative lagen triple helix, and both could conceivably cause in-frame exon both mutationsaresplicesitewithinthetype VII col assigning a diagnosis of recessive dystrophic EB. In this patient mutations, COL7A1 two has patient This recessive. autosomal are pruriginosa EB of cases of 15% Only dominant. autosomal poor genotype-phenotypecorrelation. The majorityof casesare and inheritance, of modes variable with (COL7A1), gene lagen cutaneous lesions.Itiscausedbymutationsinthetype VII col is aimedat controlling pruritus and haltingthe progression of a historyofskinfragilityandblisteringinchildhood. Treatment The onset is usually in the second or third decade of life, following forearms. and/or area pretibial the to confined typically plaques, characterised by violaceous prurigo-like or lichenified nodulesEB and dystrophic of subtype rare a is pruriginosa EB Conclusion: tacrolimus monohydrate (0.1%) ointment as maintenance therapy. resolution ofprurituswithin four weeks. Therapy wasswitched to clobetasol 17-propionate 0.05375% ointment resulted in complete compromise intron/exon splicing. Treatment and a donor splice site, respectively, and are therefore predicted to tions are sited within the consensus region ofan acceptor splice site (IVS39-aG>T) andc.7521+1G>A (IVS99+1G>A). These muta wed two heterozygous single nucleotide mutations: c.4341-1G>T negative. GenetictestingformutationsintheCOL7A1genesho was immunofluorescence Direct EB. dystrophic with consistent Investigations: Skinbiopsy showed a cell-poor subepidermal bulla knees, and knuckles. Several finger and toe nails were dystrophic. with extensive milia formation. There was scarring at the elbows, legs, lower lateral and anterior the on present were plaques and dystrophy. purpura. There wasnofamilyhistoryofskinfragilityortoenail a historyofmultiplesclerosisandimmunethrombocytopaenic shins haddevelopedoverthetenyearspriortoreferral.He with age, and resolving in adolescence. The pruritic lesions on his manifested in the neonatal period as blistering, reducing in severity with dystrophicepidermolysisbullosa(EB)ininfancy. This had pruritic lesionsonhisshins.Hehadbeenclinicallydiagnosed intensely multiple with referred was History: man old Ayear 44 1 zur Castelán, Resistencia, Chaco, Argentina, rez,Buenos Aires, Argentina, Buenos Aires, Argentina, Epidermólisis Ampollar- Facultad de Medicina, Universidad de University College Cork, Ireland, CEDIGEA - Centro de investigaciones en Genodermatosis y 1,2 1,2 Examination: Multiple violaceous hypertrophic nodules , L.Valinotto 1,2,3 2 Hospital deNiñosDr. Ricardo Gutiér , R. Andrada , 3 CONICET, 2 Department of Dermatology, 4 , S.DeFreijo 4 Hospital Pediátrico Dr. 5 Hospital Público Ma- : Daily application of 5 , G.B.Man- 3 Na------family presented the most frequent KRT5 variant (c.74C>T,p.Pro pathogenic variant (c.1649delG/ p.Gly550AlafsX77), and only one McGrath 1 Medicine, National ChengKungUniversity, Tainan, Taiwan, Medicine, National ChengKungUniversity Hospital, College of laboratory tests including reverse transcription PCT (RT-PCR),PCT transcription reverse including tests laboratory tion. Noveldisease-associatedallelic variantswerestudiedwith popula general the in frequency low sufficiently a with variants Sanger sequencingandsegregation analysiswerecarriedoutfor exome sequencingtoidentifydisease-associated allelevariants. peripheral bloodobtainedfrom EBpatientsandsentforwhole from extracted was DNA before. done not if extraction, RNA and study (IF) immunofluorescence (EM), microscopy electron histopathology,routine for performed was biopsy Skin hospital. of Taiwanese EBpatientsinNationalChengKungUniversity clinical informationincludingpreviousdiagnostictestresults tients. the genetic mutations and clinical subtypes of Taiwanese EBpa limited tocasereportsandsmallseries. We aimedtoidentify understanding ofmolecularpathology Taiwanese EBpatientsis the decades, several last the in therapy EB for research in gress pro tremendous Despite genes. 20 least in mutations by caused subtypes, clinical 30 over has EB that known now is It healing. wound abnormality and formation, blister skin, the of fragility is agroupofheterogeneousdiseases characterized bymechanical Introduction &objectives:Inheritedepidermolysisbullosa(EB) turned intoatypicalEBS-PM. afterwards and life, of years first their during phenotype ythema some ofourpatientspresentedEBSwithcircinatemigratoryer Remarkably, modifiers. molecular additional have may patients cases maybeadifferent presentationofsameEBSsubtypeorthis this phenotypes, both with associated been has c.1649delG that others hadEBSwithcircinatemigratoryerythema.Considering EBS-MP,and of features clinical typical presented patients the country. our in region specific a of from Some are they although related, not are families the pedigrees, the to According found. Conclusions: Inmostofthepatientsaninfrequentvariantwas EBS-MP, and others had EBS with circinate migratory erythema. 25Leu). Some ofthepatients presented typical clinical features of records. information was gathered through screening into patients’ medical tures ofEBS-MP wheremolecularlydiagnosed.Detailedclinical patients belonging to 12 unrelated families showing clinical fea phenotype-genotype correlations.Materials&methods:Thirty find and patients EBS-MP of diagnosis molecular Perform tive: p.Ser1306*). (c.3917C>G, gene EXPH5 in variant one p.Met119Thr) and (c.1117_1158dup42/ p.Ile373Glu386dup) and (c.356C>T,KRT14 in variants two p.Gly550AlafsX77), p.Pro25Leu), and less frequently in KRT5 domain V2 (c.1649delG/ associated to a KRT5 pathogenic variant in domain V1 (c.74C>T, moplantar keratoderma.Mostoftheworldwidereportedcasesare Wei-Ting Tu PATHOLOGY OF EBIN TAIWAN CLINICAL SUBTYPES AND MOLECULAR P71 nal ChengKungUniversity, Tainan, Taiwan, nal ChengKungUniversity, Tainan, Taiwan, ang (iWRR), NationalChengKungUniversity, Tainan, Taiwan ternational Research Center of Wound Repair and Regeneration Wan-Rung Chen UK, of Dermatology, King’s CollegeLondon(Guy’sLondon, Campus), Tainan, Taiwan, Hospital, College ofMedicine, National ChengKungUniversity, Department ofDermatology, National Cheng KungUniversity 2 , Jing-Yu Wang 4 Institute ofClinical Medicine,CollegeofNatio- Materials & methods: With informed consent, we collected Results: 3 , Peng-ChiehChen 1 , Ping-Chen Hou 2 1 School of Medicine, College of Medicine, Natio- , Sheau-Chiou Chao We foundthat11 families had an unusual KRT5 2 , Yi-Huei Wu 4,5 , Chao-KaiHsu 2 , Hsin-Yu Huang 7 , Yu-Hsiu Kuo Acta DermVenereol Suppl220 1 , Julia Yu-Yun Lee 1,6 3 5 St. John’s Institute Center of Clinical 1 Posters , Chun-LinSu 2 , Yi-Ting Hu- 1 Objec , John 6 In- 55 2 ------, Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta B. Manzur la Santísima Trinidad,la Santísima Córdoba, Argentina, 1 Juan P.Buenos Garrahan, Aires, Argentina, Angela Filoni PROSPECTIVE STUDY DYSTROPHIC EPIDERMOLYSIS BULLOSA: A CARCINOMA INPATIENTS WITH RECESSIVE ANALYSIS OF CUTANEOUS SQUAMOUSCELL MORPHOLOGICALMORPHOMETRICAL AND P73 a newgenotype-phenotypeassociationinRDEBpatients. p.Gly2653Arg variant was never associated to RDEB-I, suggesting knowledge, our of best Interestingly,the stenosis. to esophageal mucosa damagewerenotconsideredleadingtodysphagiaand esophageal and pharyngeal oral, reduce to measures Preventive EBS. as misdiagnosed clinically were they therefore and ment, Conclusions: All ourpatientspresentedmildcutaneous involve variant. p.Arg2069Cys) (c.6205C>T/ the had patient one Only cond variant was found in exon 107 (c.7957G>A/ p.Gly2653Arg). a premature stopin COL7A1 gene.Insevenofthe families the se Results: tion wasgatheredthroughscreeningintopatients’ medicalrecords. diagnosis ofepidermolysisbullosaanddetailedclinicalinforma clinical inconclusive presenting ofeightunrelatedfamilies agnosis correlations. genotype-phenotype analyze and EBS, as diagnosed clinically this workistomolecularlydiagnoseRDEB-Ipatientsthatwere of objective The anemia. and erosions corneal stenosis, canal Additional extracutaneousmanifestationsincludeexternalear lowermost portion ofthe genitourinary tract are severely affected. the and cavity,esophagus oral the mild, are manifestations skin severity ofnaildystrophyareobservedamongpatients. Although of degrees Different folds. inguinal and sub-mammary,perineal blisters form in childhood, intertriginous early skin sites, During predominantly at milia. axillary, and scars atrophic leaving heal presents withblistersanderosionsatorshortlyafterbirththat bullosa inversa(RDEB-I)isararesubtypeofDEBthatusually Introduction &objectives:Recessivedystrophicepidermolysis L. Valinotto INFREQUENT VARIANT INVERSABULLOSA ASSOCIATED TO AN RECESSIVE DYSTROPHICEPIDERMOLYSIS P72 attempt atmutationalanalysisfor Taiwanese EBpatients. scale large first the is It Taiwan.in EB of pathology molecular Our studyexpandedtheunderstandingofclinicalsubtypesand genes. COL7A1 and ITGB4, COL17A1, LAMB3, found inKRT5,were novel mutations, KRT14, LAMA3, PLEC, 24 including mutations, 44 EB. dystrophic of cases (61.7%) 29 (29.8%) cases of EB simplex, 4 (8.5%) cases of junctional EB, and 14 study,including this in included were families 31 in patients presentation andresultsofdiagnostictests.Results: subtypes andgeneticmutationsweredeterminedbybothclinical Clinical appropriate. as Westernblotting and transfection, gene 56 menico Bonamonte 1 hology, Department of Emergency andOrgan Transplantation, Gutiérrez,Buenos Aires, Argentina, Maglietta Sor MaríaLudovica,LaPlata, Argentina Human Oncology, University ofBari,Italy, nos Aires, Argentina, dermólisis Ampollar-Facultad de Medicina, Universidad deBue- Section ofDermatology, Department ofBiomedicalScienceand CEDIGEA -Centro deinvestigaciones en Genodermatosis yEpi- EB2020 1 All the families studied had one ofvariant that resulted in 2 , Giuseppina Annichiarico , 1,3 1,2,3 Materials &methods:We performed moleculardi 1 , M.Natale , Lucia Lospalluti st WorldCongressonEpidermolysisBullosa 1

2 CONICET, 1,3 , E.Cella 1 3 , Gerolamo Cicco Hospital de NiñosDr. Ricardo 3 , Leonardo RestaMD 4 4 , M.Giovo Hospital dePediatría Dr. 6 Hospital dePediatría 5 Hospital deNiños 5 2 , J.Goitia Section of Pat- Conclusions: A totalof47 1 , Antonella 2 , Do- 6 , G. - - - - pital forChildren NHSFoundationTrust, London,UK Diseases, AReS Puglia,Bari,Italy bertson search Institute, Melbourne, Australia, bourne Hospital,MonashHealthandMurdoch Children’s Re- University of Bari,Italy, lead thecSCCaggressivityinthesepatients. can dysfunction immune that assume could we diagnosis, at age well-known evolutionofcSCCinRDEBaswelltheyoungest reduction in immune cell peritumoral infiltration. Considering the sion betweenthedifferent groups. Conclusions:Ourdatashowsa expres EGFR and histology,mitoses size, of in number grading, CD4+, CD8+, CD20+, CD68+. No significant difference was found compared to controls. In particular we found a reduction in CD3+, We RDEB in infiltration immune in reduction significant a found cutaneous pseudoepithliomatous hyperplasiainRDEBpatients.Results: 5 and cSCC secondary 5 cSCC, primary 5 analysed cSCC takenby5RDEBpatientswereanalysed. As controlswe biopsies inRDEBnon-neoplasticskin.Consecutivesof The immuno-histological evaluation was performed also in skin and secondarycSCC(developedbyburnradiotherapyscars). histological difference betweencSCCinRDEBwithprimary toevaluateimmuno- Materials &methods:Theaimofourstudyis fected individuals.Immunecellsplayaroleincancerevolution. unaf than SCC developing of risk higher 70-fold a to up have to morbidity andmortalityrate.PatientswithRDEBwerereported of recessivedystrophicepidermolysisbullosa(RDEB)withahigh cell carcinoma(cSCC)isoneofthemostdevastatingcomplications by skinandmucosalfragilityblistering.Cutaneoussquamous bullosa (RDEB) is a highly disabling genodermatosis characterized Introduction epidermolysis dystrophic Recessive &objectives: with RDEB-GS(n levels weregreatestforparticipants withRDEB-GS.Individuals pain (median6.0,IQR4.0,7.6); backgroundandproceduralpain background pain (median 4.3, IQR 2.9,6.0) with greater procedural with RDEB-other. Participants in all subtypes reported significant viduals with RDEB generalised intermediate (RDEB-GI) and 29% by pain: only 19% had undisturbed sleep compared to 39% of indi (RDEB-GS) reported the greatest number of nights sleep disturbed spanning 2-4 years. Participants with RDEB generalised severe reviews four completed (65%) 31 these, Of (21%). children 10 and painatinitialreviewwereavailablefor38adults(79%)and mittee and Health Research Authority. Results: study was ethically approved by the UK Research Ethics Com The 1.0). (version Scale Itch Leuven the completed also above their sleep was disturbed by pain. Participants aged 8 years and visual analoguescale(VAS) andindicatedthenumberof nights 10cm a on changes) (dressing pain procedural and background and 6-monthly for those under 10 years. older All and participants reported years 10 those for annually reviewed were PEBLES RDEB. with individuals by reported pain and itch regarding findings preliminary report To pain. and itch including time, over them what happenstoanindividualwithRDEBandhowitaffects prospective registerstudytorecorddetailedinformationabout nowledged problemsforindividualswithRDEB.PEBLESisa ack are pain and Itch Introduction: Introduction &objectives: Eunice Jeffs OF THE PEBLESSTUDY EPIDERMOLYSIS BULLOSA (RDEB):FINDINGS WITH RECESSIVEDYSTROPHIC ITCH AND PAIN REPORTED BY INDIVIDUALS P74 College London, UK, 1 Guy’s & St Thomas’ NHSFoundation Trust, London,UK, 3 Methods: Individuals recruited to recruited Individuals Materials &methods:Methods: , JohnMcGrath 1 , ElizabethIPillay = 36) experienced more frequent itch, greater itch, frequent more experienced 36) 3 Royal Children’s Hospital, The Royal Mel- 1 , Anna EMartinez 1 , Alessandra Bisquera , Alessandra 3 Regional coordination for Rare 4 Great Ormond Street Hos- 4 , JemimaEMellerio Data regarding itch 2 , SusanRo- 2 King’s 1 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV pital forChildren NHSFoundationTrust, London,UK bertson search Institute, Melbourne, Australia, bourne Hospital,MonashHealthandMurdoch Children’s Re- in individuals with RDEB suggesting further study is warranted. appears less marked, perhaps reflecting psychological adjustment Interestingly, the impact on emotional or psychosocial wellbeing functioning. physical to relates as particularly life, of quality of Conclusions: RDEB, especially RDEB-SG, has a negative impact greater impactontheirchild’s qualityoflifethandidthechild health, with less impact for psychosocial health. Parents reported parents reportedimpactonqualityoflifewasgreaterforphysical 4 reviewsspanningaperiodofthreeyears.Childrenandtheir 7 children and their parents (64%) completed PedsQL at a further and 11 parents completed PedsQL at their initial review; of these, made tofeeluncomfortablebecauseoftheirEB.Fourchildren than othersubtypesexceptforbeingworried/anxiousand RDEB-GS reportedgreaterimpactofEBonallaspectsdailylife life, with very mild impact on emotions (≤4/15). Individuals with (5/15). Othersubtypesreportedlessoverallimpactonqualityof emotions on impact mild only but (19/36), functioning physical reported severeimpactonoverallqualityoflifescores(24/51)and three years. Adults withRDEBgeneralisedsevere(RDEB-GS) of period a spanning reviews subsequent two completed (68%) 25 and review, initial their at QOLEB completed adults seven Ethics CommitteeandHealthResearch Authority. Results: (QOLEB). The study was ethically approved by the UK Research years andabovecompleted the Quality ofLifeinEBquestionnaire Quality ofLifeInventoryversion4(PedsQL). Adults aged19 and parentsofchildrenaged2-18yearscompletedthePediatric appropriate quality oflife questionnaire. Children aged 5-18years age- an completed participants review, each At years. 10 under wed annually for those 10 years and older and 6-monthly for those methods: quality oflifeforadultsandchildrenwithRDEB.Materials& To report preliminary findings from the PEBLES study regarding both thephysicalaspectsandimpactonqualityoflife.Objective: with RDEB and how this affects them over time. This includes record detailed information about what happens to an individual milies. (1,2) PEBLES is an prospective register study designed to impact onthequalityoflifeaffected individualsandtheirfa significant a has IntroductionRDEB Introduction: &objectives: Eunice Jeffs OF THE PEBLESSTUDY EPIDERMOLYSIS BULLOSA (RDEB):FINDINGS INDIVIDUALS WITH RECESSIVEDYSTROPHIC QUALITY OF LIFEREPORTED BY P75 the benefitoffuturetherapies. common symptoms and provide a baseline against which to test They highlightthecurrentlackofeffective treatmentsforthese morbidity andimpactonqualityoflifecausedbypainitch. the confirm RDEB with individuals of cohort substantial a from findings lack ofeffectiveThese treatmentforitch.Conclusions: the by frustrated were Participants effect. treatment with tisfied (6%), althoughtheyweregenerallyambivalentorslightlydissa antihistamines (28%), emollients (22%) or a combination of both Nearly half (44%) were not using treatment for itch. Others used a commonconsequenceofitchinRDEB-GSnotothersubtypes. bad moodandlossofconcentration.Reducedqualitylifewas disturbed routine, difficulty falling asleep, being woken up by itch, individuals reported consequences of itching such as skin damage, all of half than More duration. shortest but distress, and severity College London, UK, 1 Guy’s & St Thomas’ NHSFoundation Trust, London,UK, 3 , JohnMcGrath Methods: Individuals recruited to PEBLES were revie 1 , ElizabethIPillay 3 Royal Children’s Hospital, The Royal Mel- 1 , Anna EMartinez 1 , Alessandra Bisquera , Alessandra 4 Great Ormond Street Hos- 4 , JemimaEMellerio 2 , SusanRo- Thirty- 2 King’s 1 - - - Marañón, Madrid,Spain, Unit, IISGM,TERCEL,HospitalGeneral Universitario Gregorio Fernandez-Bello lege London, UK, tre, Guy’s andSt Thomas’ NHSFoundation Trust andKing’s Col- Vicente nez-Queipo College London,UK, tology Department,LaPazUniversityHospital,Madrid,Spain, 1 L. Martínez-Santamaría BULLOSA RECESSIVE DYSTROPHICEPIDERMOLYSIS MESENCHYMAL STROMAL CELLSFOR OUTCOMES OF A PHASEI TRIAL OF SYSTEMIC PRELIMINARY SAFETY AND EFFICACY P76 1. Frew JW, et al. Br J Dermatol. 2009;161:1323-30. 2 Jeon IK, et al. Ann Dermatol. Reference 3 progress ofthediseaseandregenerative capacityoftheskin. malies associatedwith T cellscouldbekeytodetermining the infusion. first the after months 12 and 9 6, 3, 2, and baseline at performed was patients of characterisation administered every21days.Clinical,histologicalandmolecula r infusion) derived from haplo-identical bone marrow donors were total of three intravenous infusions of MSCs (2–3 million cells/kg/ and anegativeanti-C7antibodiesontheirskinwereincluded. A expression C7 minimal a with patients response, autoimmune of to 17years)wereenrolled.Inorderminimizethepotentialrisk exploratory clinicaltrialinwhich9childrenwithRDEB(aged1 patients’ responses. Methods: A single-centre, phase I, open-label, elucidate the safety and efficacy of systemic MSCs and stratify the clinical benefits are poorly understood. Our study aims to further seases. However, the therapeutic mechanism and the variability in benefits have been reported in RDEB and other inflammatory di adhesion. MSCsareusuallywelltoleratedandtransientclinical epithelial-mesenchymal improve and fibrosis, and remodeling tissue healing, wound in behaviour cellular the modulate MSCs which have remarkable anti-inflammatory(MSCs), properties. Furthermore, cells stromal mesenchymal allogeneic the is therapy complications secondary to chronic inflammation. One promising incurable inherited mucocutaneous fragility disorder with systemic due to partial or complete absence of type VII collagen (C7), is an Introduction: Recessive dystrophic epidermolysis bullosa (RDEB), FJD, Madrid,Spain, Hospital-IdiPAZ, Madrid,Spain, first twoauthorscontributedequallytothiswork IdiPAZ, LaPazUniversity Hospital, UAM,Madrid,Spain.*The nández-Santos riba promise MSCsasapotentialeffective therapyforRDEB. Ano expression C7 in increase modest a with pain and itch healing, without anyseriousadversereactions. Improvementinwound the respondingpatient.Conclusions: MSCswerewelltolerated the T cellsubpopulations. Those alterationsweremoremodestin of peripheral blood leukocyte population at baseline, particularly patients had variable but significant alterations inAll theexpression. percentages C7 in increase modest a and resistance, skin in increase an pain, and itch of alleviation as well as membranes, was an improvement in wound healing of both, skin and mucous there efficacy, Regarding skin. the in found was antibodies C7 treated withoutsevereadversereactions.Nodepositionofanti- 7 patientsenrolled(aged4to14years;1male/4females)were Cell BiologyDepartment,UCM,Madrid,Spain, U 2016;28:6-14. 714 1 -CIBERER, UC , E.Jimenez 3 , R.deLucas 7,8 , L.Liu 4 , N.Butta 5 3 , M.Carretero , M.García 3 7 2 M-CIEMAT, IISFJD,Madrid,Spain, , J.Mee , M.J.Escámez 7 St John’s Institute of Dermatology, King’s 1 5 *, R,Maseda , V. Yuste 5 Hematology Unit,LaPazUniversity 9 Clinical Pharmacology Department, 7 1 , R.DePaz , E.Chacón 8 1 NIHR BiomedicalResearch Cen- , R.Yañez 5 6 , J.A. McGrath U Acta DermVenereol Suppl220 1 715 2 *, R.Sacedón -CIBERER, CIEMAT, IIS- 5 , A. Borobia, A. 6 1 , S.M.Lwin , S.Suárez-Sancho Results: 7 Posters , M.del Río 4 3 Cell Therapy , M.C.de Ar 9 7 Five ofthe , M.E.Fer , M.Marti- 2 Derma- 1 4 , A. , I. 57 - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta pital forChildren NHSFoundationTrust, London,UK bertson search Institute, Melbourne, Australia, bourne Hospital,MonashHealthandMurdoch Children’s Re- non scarring vesicles since infancy, arising on the soles of her feet with mottledpigmentation(EBS-MP). The patient presentedwith Results: National SkinCentre, Singapore Charmaine ELim,KongYL. MOTTLED PIGMENTATION - A CASEREPORT EPIDERMOLYSIS BULLOSA SIMPLEX WITH P78 to familieslivingwithEBaswellthewiderhealthcaresystem. types. These datahighlighttheeconomicburdenofwoundcare wound and paid care is up to 30 times higher than in other RDEB of cost the impact; financial greatest the have families their and impacted. financially (25%) of those with RDEB-GI and 1 (14%) for RDEB-other were employment due to providing daily EB care, whereas only 4 carers ved unpaid care from a family member who was unable to seek INV, wound care cost ranged from £2,709 pa for RDEB inversa (RDEB- plete data, these findings are a conservative estimate. The average garments was£2,431,844;assomeparticipantsprovidedincom retention and bandages tubular dressings, wound of cost annual of 53patientswithRDEBhadaninitialreviewatwhichthetotal Ethics CommitteeandHealthResearch Authority Results: pay scale. The studywasethicallyapproved bytheUKResearch calculated at £12.50 per hour regardless of location or carer’s actual at was as care calculated paid were of and cost (£) 2017; August provision andfunding.Costsare reported per annum (pa)asGBP care regarding details and fixings, and dressings of use weekly for those under 10 years. At each review, participants reported their were reviewed annually for those 10 years and older and 6-monthly RDEB. the costofdressingsandassociatedtreatmentindividualswith treatment. fects them over time, including costs of dressings and associated about whathappenstoanindividualwithRDEBandhowitaf prospective registerstudydesignedtorecorddetailedinformation about thecostoftreatingindividualswithRDEB.PEBLESisa Introduction &objectives: Introduction: Little information exists Elizabeth IPillay STUDY BULLOSA (RDEB):FINDINGSOF THE PEBLES RECESSIVE DYSTROPHICEPIDERMOLYSIS TREATMENT COSTSFORINDIVIDUALS WITH P77 mediate respondersandnon-responders. their responsiveness to MSCs may help stratify responders, inter correlation ofthepatients’ immunologicalstatusatbaselineand patient’s inflammatory/immunological status at baseline. Further the in differences the reflect may efficacy the in variability The 58 College London, UK, 1 of £31,980 pa. Thirteen (72%) participants with RDEB-GS recei participants withRDEB-GSreceivedpaidcareatanaveragecost their dressings all at once, with patch-ups as required. Ten (56%) 39 minutes daily for RDEB-GI. Most participants (71%) changed change dressings ranged from 105 minutes daily for RDEB-GS to (RDEB-GI) and2withRDEB-INV. The averagetimetakento not require any dressings: 2 with did RDEB-generalised intermediate participants four Only costs. dressings annual total of 61% (RDEB-GS, Guy’s & St Thomas’ NHSFoundation Trust, London,UK, n = 3 , JohnMcGrath Materials &methods:IndividualsrecruitedtoPEBLES EB2020 1 5), increasing to £81,858 pa for RDEB generalised severe We describe a rare case ofepidermolysis bullosa simplex : To report preliminary findings regarding findings preliminary report To Objective: n = 18); participantswithRDEB-GSaccountedfor 1 st , EuniceJeffs WorldCongressonEpidermolysisBullosa 3 Conclusions: IndividualswithRDEB-GS Royal Children’s Hospital, The Royal Mel- 1 , Anna EMartinez 1 , Alessandra Bisquera , Alessandra 4 Great Ormond Street Hos- 4 , JemimaEMellerio 2 , SusanRo- 2 A total King’s 1 - - - - Kung University, Tainan, Taiwan ter forWound RepairandRegeneration (iWRR), National Cheng ang London, UK, stitute of Dermatology, King’s College London (Guy’s Campus), Chang Graduate School of Medicine, Sapporo, Japan, National ChengKungUniversity, Results: 2 Wei-Ting Tu EPIDERMOLYSIS BULLOSA SIMPLEX THE PATHOGENESISOF AUTOSOMAL RECESSIVE PLECTIN MISSENSEMUTATION P.LEU319PRO IN P79 processes whichcontributetotheEBS-MP phenotype. pathophysiologic possible the examine We p.Gly550AlafsX77. vealed a mutation in the V2 domain of keratin 5: c.1649_1649delG, limbs wasobserved after the erosions healed. Genetic analysis re ties tothetrunk.Reticulatebrownpigmentationonhertrunkand 1 Chung-Ching Chang ULCERS BULLOSA RELATED ORAL EROSIONS AND ORAL GLUTAMINE ALLEVIATE EPIDERMOLYSIS P80 genotype-phenotype correlationinEBS. fect ofamissensePLECmutationonproteinstabilityandextend ef detrimental the highlight studies Our p.Leu319dup. residue, different reportedpathogenicduplicationmutationaffecting this The findings for p.Leu319Prowere similar to those observed fora p.Leu319Pro, than those transfected with wild-type PLEC cDNA. with mutantPLECcomplementaryDNA (cDNA)harboring transfected HEK293 in plectin reduced significantly revealed 2. Invitrostudiesonoverexpressionofplectinandbeta4integrin c.2807G>A(p.Trp936Ter)case in (p.Leu319Pro) c.956T>C and and 1, case in (p.Leu319Pro) c.956T>C and (p.Arg2319Ter) c.6955C>Tmutations, PLEC heterozygous two revealed (WES) complete absenceofplectinlabeling. Whole exome sequencing Immunofluorescence microscopy of patient skin showed an almost obvious muscles weakness, hoarseness, ptosis, or pyloric atresia. have not did They keratoderma. palmoplantar and fingernails, and toe all of dystrophy erosions, and blistering erythematous generalized had patients Both p.Leu319Pro. variant, unreported previously a is mutation missense the cases both in mutations: patients withcompoundheterozygousnonsense/missensePLEC AR-EBSTaiwanese two describe we Here, observed. rarely are PLEC in mutations missense AR pathogenic contrast, In cause AR-EBS arenonsensemutationsorout-of-frameindels. Typically,(EBS). which simplex PLEC bullosa in mutations the epidermolysis disease, blistering inherited the of subtypes (AR) can underlie both autosomaldominant and autosomal recessive intheplectin gene(PLEC) Mutations beta4 integrinsubunit. the including proteins, hemidesmosomal and filaments diate McGrath 1 Health, National Taiwan University after minortraumaandsubsequentlyspreadingfromtheextremi versity Hospital Taiwan University, Department ofDentistry, National Taiwan Uni- National Cheng KungUniversity, Tainan, Taiwan, National Cheng KungUniversity Hospital, College of Medicine, University, Hospital, College ofMedicine, National ChengKungUniversity, School ofMedicine, College ofMedicine, National ChengKung Department ofDermatology, National Cheng KungUniversity Taipei Municipal Chenggong HighSchool, 2 , Jing-Yu Wang 3

5 Plectin is a linker-protein that interacts with interme , KenNatsuga 3 1 Institute ofClinical Medicine, College of Medicine, , Peng-ChiehChen 6 Department of Dermatology, Hokkaido University 2 , Sheau-ChiouChao 1 ClaudiaYun-TzuChang 6 , Chao-KaiHsu 3 , 4 , Ping-Chen Ho 4 3 Center ofClinical Medicine, School of Dentistry, National 1,3,7 1 , JuliaYu-Yun Lee 2 Department ofPublic 7 International Cen- 2 2 , Hsin-Yu Hu- 5 Hao-Hueng St. John’s In- 1 , John - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV 1 Del Rio (CIEMAT), Madrid,Spain de InvestigacionesEnergéticas Medioambientales y Tecnológicas removal of a mutation-containing COL7A1 exon in primary patient removal ofamutation-containing COL7A1exoninprimarypatient complexes delivered by electroporation, achieved highly efficient NHEJ-based correctionprotocol consistingofdualgRNA/Cas9 Materials &methods:We haverecentlyshownthataone-step using different genome editing tools in primary patient cells. precise and correction ofmultiplepathogenic mutationsinCOL7A1gene efficient highly achieve to is research this of goal the mostseveresubtypesofEpidermolysisBullosa. The main of one RDEB, of cause the are (C7), type collagen encoding VII gene the COL7A1, in Mutations Introduction & objectives: Bonafont DYSTROPHIC EPIDERMOLYSIS BULLOSA EX VIVOCORRECTIONOF RECESSIVE STRATEGIES FORCLINICALLY-RELEVANT CRISPR/CAS9-BASED GENEEDITING P81 of healingoralulcersanderosioninEBpatients. subjective inoralulcersanderosion.Itmayshortentheduration significantly reduce the duration and severity of both objective and pared withplacebo(p score reported, were significantly improved with glutamine com pain and erosion oral of severity and duration including vement, period (3.6 The number of oral ulcers EB patients in glutamine administrated (30%). period administrated placebo with compared as (70%) response rateofEBpatientsinglutamineadministratedperiod sion andperiodwithplacebo.Results: and werecomparedbetweentheperiodwithglutaminesuspen survey,the completing ulcer oral of severity the on influence the oral erosions and ulcers around the intervention period. After improvement inprintedformatonthedurationandseverityof subjective their record patient Furthermore, period. intervention the responseandnumberoforalulcersperiodicallyateach intervention periodfor6-weeks. We evaluatedanddocumented different at saline) (normal placebo or saline) normal ml 240 in g (10 suspension glutamine use either to randomly and blindly epidermolysis bullosawereenrolled. The patientswereallocated hods: erosion andulceroforalmucosainEBpatients.Materials&met pose of this study is to evaluate the influence of oral glutamine on who receivedradiotherapyandshownpromotehealing. The pur Oral glutaminehasbeenshowntoalleviatemucositisinpatients dysphagia, which may exacerbate the nutrition status of patients. of EB.Oralmucosaulceranderosionusuallyleadtopain bullae, ulcers, and erosions may be the most common oral feature by blisteringandmechanicalfragilityoftheskinmucosa.Oral a groupofinheriteddermatologicaldiseasesthatarecharacterized Introduction &objectives:Epidermolysisbullosa(EB)represents Biomédica enRedEnfermedadesRaras(CIBERER) U rid, Spain, in glutamineadministratedperiod(9 patients EB of ulcers and erosions oral of duration The (20%). erosions andulcersascomparedwithplaceboadministratedperiod EB patientsinglutamineadministratedperiodonseverityoforal the placeboperiod(p and number oforal ulcers were better in the glutamine period than placebo administratedperiod(12 Fundación JiménezDíaz,Madrid,Spain, M. Garcia ford, California,USA, (6.0 (UC Department of Biomedical Engineering, Carlos IIIUniversity ± 3 M), Madrid,Spain, 3.2). The objective parameter such as response rate, number From Jan 2016 through Dec 2017, 5 patients with recessive 1,2,3,5 1,2 1,2,3 , A. Mencía , A. ± 4 , R.Murillas Department ofPediatrics,Stanford University, Stan- 2.6) ascomparedwithplaceboadministratedperiod , MJ.Escamez < < 2,3 0.05). Subjective improvement (60%) of (60%) improvement Subjective 0.05). 5 0.05). , W. Srifa 2 2 Epithelial Biomedicine Division, Centro , Instituto deInvestigaciónSanitariala 3 , 5 andF. Larcher 1,2,3,4 Conclusions: Oralglutaminemay , B.Duarte 4 ± , S.Vaidyanathan 6 days).Thesubjectiveimpro ± Partial Responseandtotal 4 days)ascomparedwith 3 Centro deInvestigación 1,2,3,5 2,3,5 , MH.Porteus 4 , R.Romano 714 , Mad- 4 , M. 4 - - - - - , UK, Street HospitalforChildren NHSFoundationTrust, London,UK into clinics. approaches both of translation the enables achieved, frequencies of gene corrected bulk keratinocytes, thanks to high gene editing gene correctioncoveringawidernumberofmutations. The use precise a offers strategy HDR-based Otherwise, removal. exon could beappliedtoothermutation-containingexonssuitablefor nude mice.NHEJ-basedapproachoffers atherapeuticoptionthat support normalhealthyskinregenerationwhentransplantedonto to able efficiency correction gene remarkable offer tools editing with aclinically-relevantapplication.Conclusions:Bothgenome to restoredermal-epidermaladhesioninregeneratedskintissue in normal keratinocytes, showing that these are feasible strategies tions ofgeneeditedkeratinocytesiscomparabletothatdetected a correctedfulllenghtC7protein.expressioninbulkpopula showed efficiencies over 40% in primary keratinocytes, releasing strategy correction gene HDR-based hand, other the On C7. nal had multipletumours(mean5.8 (range1-44)).SCC-associated majority the and group, RDEB-SG the in occurred SCCs Most years)). 30-89 (range years 47.1 (median collectively groups group (median29.5years(range 13-52years))comparedtoother RDEB-SG the in earlier was SCC first of Diagnosis syndrome. (11.4%) with dominant dystrophic EB, and 1 (2.3%) with Kindler 5 (JEB-GI), intermediate generalised EB junctional with (6.8%) inversa (2.3%), 2 (4.5%) with RDEB-generalised intermediate, 3 RDEB- with 1 RDEB-pruriginosa, with (2.3%) 1 with RDEB-SG, (70%) 31 comprised: They SCCs. primary 221 of total a Results: EB patients diagnosed with SCC between July 1991- June 2019. of review record case institution double retrospective, vational, SCCs overthelast28years.Materials&methods:Anobser adulthood. We report our centres’ experience of EB-associated aggressively andarethemajorcauseofmortalityinearlytomid- mucocutaneous squamouscellcarcinomas(SCCs)whichbehave (RDEB-SG), are associated with an increased risk of developing EB dystrophic recessive generalized severe notably (EB), losa Introduction & objectives: Some forms of epidermolysis bul 1 Susan J.Robertson, RETROSPECTIVE STUDY IN EPIDERMOLYSIS BULLOSA: A 28 YEAR CUTANEOUS SQUAMOUS CELL CARCINOMA P82 vin O’Sullivan practically everycellinthebulkpopulationexpressingfunctio exon removal close to 90% in primary RDEB keratinocytes, with Results: enabling HDR-basedcorrectionforawiderspectrumofmutations. potentially gene, COL7A1 of exons 10 covers design template donor This gene. the correct AAV,carrying precisely to aiming to createdoublestandbreaksintheDNA andadonortemplate- free HDR-based strategy for RDEB correction, using Cas9 as RNP number of patients. On large the a other hand, for we benefits have the designed a spreading marker gRNAs, of pair the changing adapted tootherexonsoftheCOL7A1collagenousdomainby of SpanishRDEBpatients). This exonremovalstrategyhasbeen (46% population RDEB Spanish the in prevalent highly is exon this in mutation frame-shift a because target a as chosen was 80 that canbegraftedontoaffected skinofRDEBpatients.Exon patient keratinocytescouldbeusedtogenerateskinequivalents strategy,gene-corrected correction keratinocytes. Inthisexvivo blatt Jemima E.Mellerio Australia, Monash Health, Murdoch Childrens Research Institute, Melbourne The RoyalChildren’sHospital, TheRoyalMelbourne 2 3 , Catina Bernardis Brighton GeneralHospital,ESussex,UK, Forty-four EB patients with SCC were identified with identified were SCC with patients EB Forty-four With the NHEJ approach, we achieved efficiencies of efficiencies achieved we approach, NHEJ the With 2 Guy’sand StThomas’ Foundation Trust, NHS London, 2 , JessieFelton 2 1

Elizabeth Orrin 2 , John A. McGrath 3 , Alistair Robson,Danielle T. Green- Acta DermVenereol Suppl220 2 , Manpreet KLakhan 2 , Anna E. Martinez Posters 4 Great Ormond 2 , Ga- 59 4 - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Santa Catarina,Brazil for metastatic disease included lymph node dissection ( Treatments JEB-GI. with 1 and patients RDEB-SG (51.6%) 31 of 16 in occurred disease Metastatic (86.4%). tumours of rity extremities. Wide localexcisionwasundertakenforthemajo the on located and (53.4%) well-differentiated were SCCs Most years). 0.5-12.6 (range years 2.4 of SCC first of diagnosis after mortality was high in this group (64.5%), with a median survival www.medicaljournals.se/acta Table 1.Summaryofkeysurveyresults and Brazil.OverallPV “A”scoredhighlyonthemeasuresof Belgium, Australia, UK, Ireland, Norway, Singapore, Netherlands, PPI, six were clinical experts, and one was both. They represented a PVsfeedbackSurveyHerolink.Results: Evidence (DECIDE)project1. Their feedbackwascollectedusing tion StrategiestosupportInformedDecisionandpracticebasedon and keythemesfromtheDevelopingEvaluatingCommunica model group. honeycomb each the using Amodified was survey the CPGnetworkwereinvitedbyemailtoreviewonePV from external experts in EB, experts in PV development, and PPI from that produced four user-targeted PVs. In August-September 2019 panel ofexperts,peoplelivingwithEB(PPI),andadesignteam of only clinical staff focussing onone PV and the other was a mixed to develop PVs for their published guidelines: one panel consisted requirements. development methods to determine what met the EB Community’s demand forthem. The objectivewastoreviewtwodifferent PV information orPVsastheyacknowledgethatthereisanincreasing patients. Internationalguidelinedevelopersareproducingpatient delines (CPGs)wouldhavebeendevelopedwithoutthedriveof unlikely thatpatientversions(PVs)oftheclinicalpracticegui is organisation,it patient a for undertaking unusual an Although plex condition that affects the skin and many parts of the body. Introduction &objectives:Epidermolysisbullosa(EB)isacom Kattya M.Mayre-Chilton WITH EPIDERMOLYSIS BULLOSA PRACTICE GUIDELINESFORPEOPLELIVING IMPROVING PATIENT VERSIONS OF CLINICAL P83 1 Hospitals NHSFoundationTrust, London,UK, radiotherapy (n need formoreeffective treatmentsforthisdevastatingcondition. or 4th decade forother at-risk groups. It also highlights the pressing patients, starting from adolescence in RDEB-SG and from the 3rd reinforce theneedforregularclinicalsurveillanceSCCsinEB data our date, to management and course clinical regarding data As thelargest cohortofEBSCCpatientswithcomprehensive of just2.4yearsunderscoresthepoorprognosisinthisgroup. median survival after diagnosis of first SCC in RDEB-SG patients metastasise earlydespitewell-differentiated histopathology. The there areoftenmultipleprimaries. They behaveaggressivelyand and group age younger a affect they population: general the in cemiplimab. tolerated, however were limited in response with the exception of (n (n 60 Participants completesurvey Patient version(PV) Types ofEB representation information on Did thePV coveralltopicstheywanted Positive feedback DEBRA International,Vienna, Austria, = = 2) andcemiplimab(n (n erlotinib therapies targetedcancer and 2), EB2020 1 Conclusions: EB-associatedSCCsdiffer fromthose Materials &methods:Two CPGpanelswereinvited = st 5), chemotherapy (n chemotherapy 5), WorldCongressonEpidermolysisBullosa 1,2 = , OliviaMullins A 6 Dystrophic EB 100% Yes thoroughly described and areveryuseful parts All 1). Treatments weregenerallywell- = 3), electrochemotherapy 3), 2 Eight participants were Eight participantswere 1 Guy’sand StThomas’ , Lie A. Taguchi B 9 and DystrophicEB EB Simplex, Junctional EB, 56% Yes boxes ‘Recommendation’and tips photos, quotes, Patient 3 = DEBRA Brasil, 1), cetuximab 1), 1,3 n =

6), - - - - 1 Moksha ManishShah DISEASE INRDEB-LINKEDSCCS MIR-10B AS A MARKERFORDISSEMINATED P84 1. Fearns et al. Improving the user experience of patient versions of clinicalguideli decision-making andsupporttheinternationalEBCommunity. simple while providing sufficient information to facilitate shared we needtoreachtherightbalancebetweenkeepingEBPVs want from them. As a “one size fits all” approach is not possible, people livingwithEBknowaboutCPGsorPVsandwhatthey linked toEB-focussedCPGs. We are startingtounderstandwhat There isgenerallyalowlevelofaccessandawarenessPVs ting. The summaryofresultscanbeseenin Table 1.Conclusions: ‘Findable’in poorly ‘Accessible’and ra star 4-5 given were but on the information coming from ‘Credible Sources’. Both scored rable’, ‘Usable’, ‘Useful’, and ‘Valuable’. PV “A” scored poorly ‘Useful’‘Valuable’and ‘Desi in highly scored “B” PV whereas detecting circulatingtumorcells (CTCs)inthebloodofpatients filtration-based (Creatv Microtech, CellSieve System) methods of with mRNAs of localisation specific cell in methods combining potential toavoidtraumaticskin biopsies.Inourlaboratoryby in RDEB-linkedSCCsisparticularly attractivebecauseithasthe liquid biopsy(blooddraw)for diagnosing disseminateddisease miR-10b. express that cells tumor methods for analysis of blood of RDEB patients for disseminated node metastasesfromRDEB-linkedSCCs;andbegunoptimizing found that miR-10b is up-regulated in primary tumors and lymph also Wehave keratinocytes. control normal to compared SCCs, lated inprimarycelllinesisolatedfromSCCsandRDEB-linked House , Salzburg, Austria, we have identified miR-10b as up regu Reports]. Scientific (2015) al. et [Gasch biopsy) (liquid patients cancer of small RNAsindisseminatedcancercellsisolatedfromtheblood hybridization that have allowed situ for the in cell fluorescent specific localisationin of methods developed we work, previous In of enzyme(RNase)degradationtheyarealsoremarkablystable. Importantly for diagnostic purposes, as they are the end products sion can be indicative of significant changes in disease pathology. cell differentiation anddevelopment. ChangesinmiRNA expres as markers of malignancy in cancer. miRNAs are key regulators of begun workinvestigatingtheuseofsmallRNAs(micro/miRNAs) healing. given that patients already have significant problems with wound screening. In EB patients such screening is especially problematic regular encourage not do biopsies, skin traumatic involve which time between the diagnosis andshorten treatment. to However, current need methods, great a is there Consequently, population. more aggressive than SCCs appearing in an otherwise healthy death sentence. SCCs from RDEB patients tend to be significantly trophic epidermolysis (RDEB), the diagnosis of an SCC can be a most SCCs are curable. However, for patients with recessive dys early,(NMSC). caught cancer When skin nonmelanoma of form second most common form of skin cancer, and the most common Introduction &objectives:Squamouscellcarcinoma(SCC)isthe University ofWollongong, Wollongong NSW, Australia, lick Mila Sajinovic Salzburg, Austria Austria, University Hospital ofthe Paracelsus Medical University, versity of NewSouthWales, LiverpoolNSW, Australia, improved Could the layout and/or language be Require contentinanotherlanguage Ingham Institute for Applied Medical Research, Medicine, Uni- version BMCHealthServicesResearch(2016)16:37 patient (SIGN) Network Guideline Intercollegiate Scottish a of testing user nes: 1,2 Materials &methods:In the last couple of years, we have Results: 1 , Paul De Souza In collaboration with the Wally Laboratory, EB 1,2 , Hannelore Bodocian 67% Yes 83% Yes 1,2 , Verena Wally Conclusions: The useofthe 1,3 33% Yes 56% Yes , RolandZauner 3 , Albert S. Mel- 3 2 EB House Medicine, 3 ------, Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV City, Riyadh, Saudi Arabia, 1 versity of Tokyo, Tokyo, Japan, Animal Research Center, InstituteofMedicalScience, The Uni- ta single-component Class 2 CRISPR systems, such as Cas9, are Cas9, as such systems, CRISPR 2 Class single-component tems aretaxonomicallygrouped asClass1and2. Although adaptive immunesystem in prokaryotes. The CRISPR-Cas sys palindromic repeats(CRISPR)-CRISPR associated(Cas)isan Introduction &objectives: Clusteredregularlyinterspaced short Hiroyuki Morisaka DOMINANT EPIDERMOLYSIS BULLOSA NOVELSYSTEM FOR CRISPR-CAS3 AUTOSOMAL UNIDIRECTIONAL GENOME EDITING USING THE POSSIBLE APPLICATIONBROAD AND OF P86 genetic disorder. spectrum of the genetic profile and to prevent future of such rare propose anationwideEBprogramthatwouldhelptoextendthe to thecommonconsanguinitylevelamongSaudipopulation,we and we identified 14 novel mutations previously not detected. Due the mostfrequenttypeassociatedwithCOL7A1genemutations was DEB Arabia. Saudi in profile genetic EB of report first the heterozygous mutations.Conclusions: To ourknowledgethisis Only threecaseswerefoundtobeautosomaldominantdisplaying mutations. homozygous of presence by confirmed and history consanguinity positive documented were cases EB of (87.5%) majority Furthermore, (14.3%). 4 in TGM5 and (17.9%), 5 in LAMB3 by followed COL7A1 of (42.9%) 12 in detected were and ofwhich14werenovelmutations.Mostfrequentvariations 24 variousgeneticvariationsdetected among EB associatedgenes revealed result genetic molecular The JEB. (21.4%) 6 and EBS, thirteen (46.4%) of which were with DEB followed by 6 (21.4%) databases. Database (gnomAD)andExome Aggregation Consortium(ExAC) ants were checked against HGMD, ClinVar, Genome Aggregation custom design AmpliSeq panelofgenes. All disease-causingvari analysis wasdonebytestingpatients’ genomicDNA usinga technique wasusedtoapproachallaffected patients.Molecular ter, Riyadh, Saudi Arabia. Consecutive non-probability sampling study targeting patientswithEBregisteredinourtertiarycarecen methods: of SaudiEBpatientsatatertiaryhealthcarecenter. Materials& profile genetic To(EBS). the simplex explore EB and (JEB) EB junctional (DEB), EB dystrophic into classified be can and sive reces dominantoranautosomal anautosomal may beinheritedas skin fragilityleadingtoblisterformationafterminorinjuries.EB genetic mechano-bullous skin disorderscharacterized byincreased Introduction &objectives:Epidermolysisbullosa(EB)isarare Raghad Alharthi RIYADH,ARABIA SAUDI CASES INKING ABDULAZIZ MEDICAL CITY, GENETIC PROFILEOF EPIDERMOLYSIS BULLS P85 tool thatcanaidindiagnosisofmalignantSCCSEBpatients. we hopethatwillbeabletoprovideanobjectiveandeffective seases, OsakaUniversity, Osaka,Japan. and Genetics,King Abdulaziz MedicalCity, Riyadh, Saudi Arabia. 1 mutiri University, Kyoto,Japan, Application (CiRA), DepartmentofLife Science Frontiers, Kyoto Saudi Arabia, versity, Kochi,Japan, College of Medicine, King Saud bin Abdulaziz University, Riyadh, Department ofDermatology, KochiMedical School, KochiUni- 3 , JunjiTakeda 1 , Sultan Alkhenaizan , This was an observational, retrospective chart-review retrospective observational, an was This Results: 2 Dermatology Division, King Abdulaziz Medical 4 1 , Tomoji Mashimo , Muhannad Alnahdi , 1 , Kazuto Yoshimi A cohortof28EBcaseswerecollectedand 2 Division of Animal Genetics,Laboratory 2 4 , Mohemmed Al Balwi Research Institute for Microbial Di- 3 Department ofMolecular Pathology 3 Center for iPS Cell Research and 2 andShigetoshiSano 2 , Yuya Okuzaki 1 , AhadAlharthi 3 3 , Akitsu Hot- , Akitsu 1 , Seba Al- , 1 - - - - Chang 1 versity Hospital Taiwan University, DepartmentofDentistry, National Taiwan Uni- no activity.no iden we sequencing, capture array-based Custom In or withcrRNA targeting different spacersequencesalsoshowed complete lossofactivity. Multiple Caseffectors withoutcrRNA negative control. The absenceofanyCaseffector resultedina Results: targeted COL7A1 gene in primary fibroblast with CRISPR-Cas3. we bullosa, epideromolysis for therapy to applied syastem Cas3 1-Mb regionoftheEMX1gene. To assesswhethertheCRISPR- array-based capture sequencing with 2,000–2,300× coverage of a endogenous EMX1geneinhumancells. We conducted custom targeted we patterns, deletion Cas3 characterize To cells. 293T lipofection of Cascade, Cas3, crRNA, and reporter plasmids into moter. The luciferaseactivityweremeasured24hoursafterthe E. coliwereindividuallycloneddownstreamoftheCAGpro codon-optimized Cas3, Cas5, Cas6, Cas7, Cas8, and Cas11 from recombinationassay.based single-strandannealing(SSA) Human type I CRISPR-Cas system in human cells, we used a luciferase- Materials &methods:To assesstheDNA cleavageactivityofthe crRNA, mediates distinct DNA cleavage activity in human cells. composed of Escherichia coli Cascade, Cas3, and programmable cleave foreign DNA. Here, we demonstrate that type I-E CRISPR, endonuclease, which is recruited upon target binding by Cascade to Cas3 a and (Cascade), defence antiviral for complex associated CRISPR- termed complex, multiprotein (crRNA)-bound RNA The Class 1/Type ICRISPRsystem functions as a CRISPR tion ofmulti-componentClass1CRISPRhasyettoberealized. care program, including the adequate supplements of fluoride, of supplements adequate the including program, care in a medical centre were recruited for analysis. Since 2015 an oral 2019 to 2010 between treatment dental received patients bullosa with Epidermolysis bullosa. investigate theeffectiveness oftheoralcareprogramforpatients cations andimprovequalityoflife. The purposeofthisstudyisto compli in Taiwanthese 2015 reduce since to care health oral in status. An oralcareprogramwasdevelopedtoassistEBpatients blister lead to pain and of dysphagia, which rupture may exacerbate following nutrition erosion mucosa and gingivitis, advanced intestinal tracts. Oral manifestation such as rampant dental caries, respiratory,gastro the and involve also may forms severe more anywhere on the surface of the skin, within the oral cavity and in in anchoring between the epidermis and dermis. Blisters can form by blisteringandmechanicalfragilityoftheskinduetoadefect a groupofinheriteddermatologicaldiseasesthatarecharacterized Introduction &objectives:Epidermolysisbullosa(EB)represents Chung-Ching Chang BULLOSA: ATAIWANESE PERSPECTIVE QUALITY OF PATIENTS WITH EPIDERMOLYSIS ORAL CAREPROGRAMIMPROVES THE LIFE P87 from theClass2CRISPRsystem. unique genomeeditingtoolin eukaryoticcells inamanner distinct and novel a as serve may which system, CRISPR 1 Class the of epidermolysis bullosa. These findings broaden our understanding dominant autosomal as such inheritance, dominant autosomal of dominantnegativemutationsto attenuate skindiseaseswith skipping exon induces it that so CRISPR-Cas3, by introduced cing. edited clonesweredetectedPCRgenotypingandsangersequen genome several fibroblasts, primary of treatment CRISPR-Cas3 long stretchofthetargeted regionupstreamofthePAM. After a through deletions large Cas3-mediated of variety wide a tified Health, National Taiwan University, widely used for genome editing in eukaryotic cells, the applica the cells, eukaryotic in editing genome for used widely Taipei Municipal Chenggong HighSchool, Conclusions: Large deletionsofmutated allelewouldbe 3 CRISPR-Cas3 systemshowedhigherSSA activitythan 1 , ClaudiaYun-TzuChang Materials & methods: Acta DermVenereol Suppl220 3 School of Dentistry, National 2 Department ofPublic Posters 2 Epidermolysis Epidermolysis , Hao-Hueng 61 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta treatment ofCol7a1-/-RDEBmice withFnAbsincreasestheir antibodies remainatthesiteofinjury foratleast7days.Systemic and improvehealingofmultiple woundssimultaneously. The Systemically administeredFnAbs localisetothesiteofinjury increasing themeansurvivalrate from8to17days.Conclusions: FnAb from birth significantly improved the lifespan of these mice Col7a1-/- nullRDEBmicewefoundthatdailyIP injectionsof wound areaswhichwasmaintainedupto7dayspost-injury. Using administered FnAbs showed localisation of the antibody to the ofsystemically analysis Biodistribution re-epithelialisation. wound microscopic woundareaandlengthaswellimproved saline orIgGcontrolsasevidencedbyreducedmacroscopicand resulted in significantly improved healing responses compared to Col7a1-/- RDEB mice. ned theeffect ofsystemicFnAbadministrationonthesurvival biodistribution in this in-vivo wound model. Finally, we determi Using fluorescently-labelled FnAb we further investigated FnAb (IP) of FnAb, saline or IgG control, at the time of injury, on healing. type miceweinvestigatedtheeffect ofintraperitonealinjections Materials &methods:Usinganincisionalwoundmodelinwild- systemically-administered FnAbscouldimprovehealinginEB. skin improveshealingoutcomes. This studyaimedto exploreif tion ofFlii-neutralisingantibodies(FnAb)tomurineblistered of EBpatientsandimpairshealingwounds. Topical applica Flightless I(Flii)isincreasedinblisteredskinofallsub-types that demonstrated have studies Previous fibrosis. and blistering Bullosa (RDEB)isachronicinheritablediseaselinkedtosevere Introduction &objectives:RecessiveDystrophicEpidermolysis South Australia,Adelaide of University Regenerative Medicine Laboratory, Future Industries Institute, Natalie E.Stevens,ZlatkoKopecki, Allison JCowin MURINE WOUNDS PROMOTE HEALINGOF MULTIPLE INCISIONAL EPIDERMOLYSIS BULLOSA MICE AND SURVIVAL OF RECESSIVEDYSTROPHIC I NEUTRALISING ANTIBODIES IMPROVE SYSTEMICALLYFLIGHTLESS ADMINISTERED P88 of foodintakeandsatisfythepatients. and periodontal status condition, therefore, improve the situation of dental caries and improvement of the oral hygiene maintenance frequent periodicsurveillancehadpositiveeffects onthereduction and technique, brushing well-executed fluoride, of supplements intervention. Patient also show less pain and frequency of dysphagia following comparison betweenthepreinterventionandinterventionperiods. oral hygiene index, and community periodontal index (CPI) while difference (p ween the preintervention and intervention periods. The significant 0.05. at fixed p-value with to used were t-test and the preinterventionandinterventionperiods.One-way ANOVA periodontal index(CPI). These indexeswerecomparedbetween community using assessed was condition periodontal and index, hygiene oral by evaluated was status hygiene oral Teeth)index, Filled Missing, (Decayed, DMFT by assessed was experience health carewereemployed.Foreachpatientwhosedentalcaries dental reviewbasedonDEBRA clinicalpracticeguidelinesonoral periodic frequent and technique, brushing Bass the of execution 62 slow downduringtheinterventionperiodswhilecomparisonbet leukoplakia (20%) was noted. The increments (40%), of the trismus DMFT index (50%), hypoplasia enamel including patients, junctional EB. The incidenceoforalmanifestationamongthese from suffered one and type simplex EB from suffered one type, males) weresurveyed.Eightpatientssuffered fromEBdystrophy patients with age between 6 and 35 years old (7 females and 3 EB2020 1 Conclusions: Oral care program, including adequate = 0.01 and 0.01 st WorldCongressonEpidermolysisBullosa Results: p = 0.05 respectively) was noted in the in noted was respectively) 0.05 Systemic administration of FnAbs Systemic administration of FnAbs Results: Ten - - - Krämer de Odontología,Universidad Chile training orevidence based models to direct assessment orinterven population in practice. VeryEB the few clinicians reported have with specific puberty addressing not reported 58% while all, at sexual participation in practice with 36% not addressing the topic from clinician surveys revealed awide rangeofcomfortin address themes Key presentation.Conclusions: ofthis direct theemphasis to findings significant and themes for evaluated were survey’s both from Results responses. some omitting 37 responses, 112 omissions. The surveyforindividuals livingwithEBreceived Results: of allinvolvedtoreachthegreatestnumberparticipations. International andthroughtheprofessionalsocialnetworks from Debra Norge. The survey was distributed through Debra Funding for this, as well as the larger CPG project, was received and logisticaloversightwasprovidedbyDebraInternational. achieved onallquestionsandformatpriortodistribution.Ethical thirteen researchers (8 clinical, 5 living with EB) with consensus guideline development. The surveywasdevelopedbyateamof survey developedanddistributedintheprocessofclinicalpractice This presentationreportsdatacollectedfromaneedsassessment and clinicianssupportingpeoplewithEB.Materials&methods: preliminary data and perspectives fromindividuals living with EB conversation relatedtosexualparticipationandEBbysharing of sexualparticipation-relateddata. This presentationseeksopen Epidermolysis Bullosaisaconditionforwhichtherepaucity condition, rare a As impairment. health-related or functional a ding andinterventionskillstoaddresssexwhenitisaffected by mands thatthemedicalcommunitydevelopgreaterunderstan de participation sexual of complexity and variability,vitality, Introduction &objectives: The growingunderstandingofthe Phoenix Children’s Hospital,USA Alex King,CCLS,CTRS,OTR/L ON THE TOPIC OF SEX:IT’SREAL,LET’S TALK P89 3 1 María JoaoYuberoMD G, PSEUDOMONA AERUGINOSA EPIDERMOLYSIS BULLOSA INFECTED WITH PROGNOSIS OF PATIENTS WITH P90 addressing sexualparticipationforpeoplelivingwithEB. required toprogresstowardcliniciancompetencyandcomfortin Further investigation of specific needs and intervention options is to self-confidence/comfort and communication with their partner. experiences andrelationshipsgreatlyattributedthatsuccess respondents highlightedtheirachievementofsuccessfulsexual puberty and sexual participation arose as well. Finally, numerous related complications and increased information/education around for increased support to manage psychosocial, physical, and pain- self, physical restrictions, and lack of confidence. Themes of desire about feelings reactions/thoughts, others’ of fear pain/injury, of respondents. Mostcommonbarriers toparticipation related tofear physical adaptations, and timing/planning were endorsed by many partners, sexual educating lubrication, including participation sexual improving of methods specific included EB with living tion forsexualparticipation.Keythemesinthesurveypeople the managementofEB-relatedwoundsandblisters. and may be a potential new and effective treatment strategy for lifespan suggestingthatFnAbsreducethesymptomsofRDEB na, Clínica Alemana Universidad delDesarrollo, Santiago, Chile, Alemana Universidad del Desarrollo, Santiago, Chile, Centro deGenética y Genómica,Facultad de Medicina, Clínica Fundación DEBRA Chile,Santiago, Chile, 4 , ConstanzaFuentes,MD The clinician survey received 63 responses, 23 with 23 responses, 63 received survey clinician The 1,2 , IgnaciaFuentes,PhD 1 , FrancisPalisson,MD 2 Facultad de Medici 3 , Susanne 4 Facultad 1,2 . - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV (SA) grew in 131 (83%), Pseudomonas aeruginosa (PA) in 56 in (PA) aeruginosa Pseudomonas (83%), 131 in grew (SA) patients hadcultureswithnogrowth only. Staphylococcusaureus patients had at least onepositive culture result. The remaining 6 culture resultswererecordedfor thesepatients.152outof158 one woundculturerecordedinthe database. A totalof739wound 2001 and2017wasperformed.Results:158patientshadatleast between capturedinthedatabase from158patients culture results analysis of wound cultures. A retrospective analysis of 739 wound States andCanada. Access tothisresourceenabledbroadscale of informationfromEBpatientsatmultiplecentersintheUnited tion andOutcomesDatabase(EBCCOD)servesasarepository available. centers, including methicillin and mupirocin susceptibilities, when analyzing woundcultureresultsfromEBpatientsmultiple fect thewoundsofpatientswithEpidermolysisbullosa(EB)by to improveourunderstandingofwhatmicrobescolonizeandin squamous cell carcinoma (SCC) in a subset of patients, wound-associated we sought of development the in inflammation induced Introduction &objectives:Giventhepotentialroleofbacteria- versity IrvingMedicalCentre (Morgan Stanley Children’s HospitalofNewYork), ColumbiaUni- NewYork-Presbyterian/Columbia University Medical Centre MD, JohnC.Browning, MD,MBA,KimberlyD.Morel, MD. Diaz, MD,Lucia MD, Sharon A. Glick, MD, Amy S.Paller, MD,HarperN.Price, L. Levy, Moise MD, Eichenfield, F. Lawrence Karen Wiss,MD, CatherineC.McCuaig,JuliePowell, MHA, ElenaPope,MD,MSc,IreneMD, MSc, Lara-Corrales, MD, MPH/MSPH, Susan Whittier, PhD, Christine T. Lauren, MD, Kristen P. Hook,MD, Anna L.Bruckner, MD,JamesFeinstein, Laura E.Levin, MD, Leila H. Shayegan, BA, Anne W. Lucky, MD, MULTICENTER DATABASE EPIDERMOLYSIS BULLOSA:RESULTS FROM A CHARACTERIZATION OF WOUND MICROBESIN P91 other markersthathelpusinthedeterminationofinfection. Find days. 21 of minimum a with fibrosis cystic with patients in as be should aeruginosa, Pseudomona isolating when treatment first the Perhaps death. of chance greater 40% a generates tion between the different C-protein samples, with a with ap difference between the different sedimentation rates of the samples, baumannii and Proteus mirabilis. There is no significant statistical pneumoniae, Klebsiella albicans, Candida aureus, Acinetobacter Staphilococcus Methicilin-resistant aeruginosa, Pseudomona aureus, Staphylococcus of strain Methicillin-susceptible were: 6 insomesamples.Ourmostfrequentisolatedmicroorganisms to up have to got we but culture, per microorganism 1 obtained mostly We 54.98. of prevalence a with aureus, Staphilococcus rent typesofmicroorganisms wereisolated. The mostfrequent patients. deceased from are samples 181 years). 60.95 to newborn (from from women and 188 samples were from men. Average age 10.75 were samples 314 patients. 70 from collected were samples 502 were reviewed. Registration goes from 05/09/2005 to 12/23/2015. of skin cultures, registered in the electronic file of our institution, isolates ofourpopulation.Materials&methods:Alltheresults a diagnosticaid. And toknowthemicrobiologyofwound bed intheliterature.Findoutifinfectiousscreeningtestswere know ifourmicroorganisms werethesameisolatesanddescri Introduction &objectives: The objectiveofthisreviewwasto aeruginosa ofpoorprognosis.ButPseudomonainfec Being colonizedwith Acinetobacter baumanniiandPseudomona or evenwhitebloodcellcountdoesnotcorrelatewithinfection. protein C-reactive rate, sedimentation Requesting Conclusions: = Results: 0.1739. There is no statistically significant difference significant statistically no is There 0.1739. Materials &methods:TheEBClinicalCharacteriza 83% of the samples were positive. 32 diffe 32 positive. were samples the of 83% p = 0.8023, (T test). - - - - - C. Prodinger BULLOSA TYPE RECESSIVEDYSTROPHICEPIDERMOLYSIS OTOLOGICAL COMPLICATIONS ININVERSA P92 aggressive treatment. more earlier, require may therefore and carcinogenesis for risk patients mayhelptoisolatethosebacteriathatconferadditional understanding ofwhatmicrobesarecolonizingthewoundsour improved SCC, wound-associated of development the in mation patient groupwithearlyreferral toanENT specialist. clinicians shouldbevigilantin monitoring for eardisease in this the therapeutic challenges and impact on patients’ quality of life, lence is higher than previously published studies. Considering preva This complications. otological relevant displayed (45%) 9 database, our in identified EB of form this with patients 20 the We observedahighprevalenceofearproblemsinRDEB-I.Of hearing aids(BAHA)withfavourableoutcomes.Conclusions: in 5 (56%) patients. Three (33%) patients received bone anchored loss, with conductive hearing loss confirmed by audiology testing the externalauditorycanals. All 9patientscomplainedofhearing (78%) had meatal stenosis and 5 (56%) had recurrent blistering of all havingsuffered fromrecurrentepisodesofotitisexterna.Seven le; mean age 47.3, range 31-72 years) had otological complications, from our database. Nine adult patients (45% of cohort; 89% fema COL7A1. basis of clinical features, family history and mutation analysis of the on established was Diagnosis 2019. June and 2000 January with RDEB-Ipresentingotologicalcomplicationsbetween retrospective, single institution case record review of adult patients morbidity. hort of RDEB-I patients, revealing a high prevalence of otologic limited inthispatientgroup.Hereinwecharacterizeanadultco this clinicalentity. Literature dataonearcomplicationsishighly sense mutationsinthecollagen VII triple helixmaygiveriseto mis recessive specific that postulated been has It involvement. mucosal marked and flexures body in blistering predominant dystrophic epidermolysisbullosa(RDEB-I)ischaracterizedby Introduction &objectives: The rareinversaform ofrecessive 1 counseling. Given the important role of bacteria-induced inflam resistance asameanstoguideantibioticstewardshipandpatient supports surveillancecultureswithroutinetestingformupirocin EB, with individuals in agents antibiotic topical and systemic many to Resistance respectively. tested, patients the of 40% and 47% in reported were resistance mupirocin and Methicillin commonly isolatedbacteriafromwoundculturesinEBpatients. respectively. cases, of 20% and 50% 90%, in species PAProteus SA, and for positive results culture wound documented had 10 which of patients, 22 susceptible and6weremupirocinresistant.SCCwasreportedin mupirocin 11were testing, susceptibility SAmupirocin for with positive cultures 15 Of (MRSA). SA methicillin-resistant 47% SAmethicillin-sensitive were 68% susceptibilities, and (MSSA) 117 patientswithSA positivecultureswithrecordedbeta-lactam (35%) and Streptococcus pyogenes (GAS) in 34 (22%) patients. Of G. Petrof lia, Health, Murdoch Childrens Research Institute, Melbourne Austra- al Children’s Hospital, The RoyalMelbourneHospital, Monash for Children NHS FoundationTrust, London,UnitedKingdom, dation Trust, London,UnitedKingdom John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foun- of theParacelsusMedicalUniversity, Salzburg, Austria, Department ofDermatologyand Allergology, University Hospital 3 Department ofDermatology, GreatStreet Ormond Hospital 3 , A.E. Martinez , A.E. Results: Materials & methods: We conducted an observational, 1 , S.J.Robertson Twenty patients with RDEB-I were identified Conclusions: SA andPA werethemost 3 , D.Greenblatt 2 , S.Chottianchaiwat Acta DermVenereol Suppl220 4 , J.E.Mellerio Posters 3 , M.Laimer 4 2

The Roy- 4 63 St 1 - - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta of life, where he was diagnosed of Herlitz junctional EB (HJEB), to worsening of the lesions, he was referred to our centre at 44 days bullous pemphigoid.Duetothe lack ofresponsetotreatmentand hylococcal scaldedskinsyndrome andsubsequentlyasneonatal extensive blisteringoftheskin. HewasthendiagnosedasStap developed rapidly patient the days, following the In blisters”. “suction as hospital local his at diagnosed were which thumbs, both on bullae few a life of hours first the within developed who case whichwasmisdiagnosed. We presentthecaseofamaleinfant awareness aboutthisconditionthroughthepresentationofafatal unknown bymosthealthcareprofessionals;ouraimistoraise Results: Juan CarlosLópez-Gutiérrez Muñoz-Serrano, Mercedes Díaz,Rocío Maseda, RaúldeLucas, Carlos Delgado-Miguel, Miriam Miguel-Ferrero, Antonio J. ON PATIENTS AND THEIR FAMILIES MISDIAGNOSIS INEB: YET ANOTHER BURDEN P94 program forpatientswithEBsimplex. become anewlyconsideredtreatmentoptionaspartoftailored sions: The studysofarindicatesthatrockerbottomfootwear could altered blisteringsitesandincreasedactivityasaresult.Conclu blistering, overall in reduction scores, pain in reduction a shown centre ofmassdisplacement.Earlyquestionnairefeedbackhas biomechanical progressionincludingpeakplantarpressuresand in alteration significant a showed pressures after and before of andfootwear. insoles more standardised Results: questionnaires have been completed by subjects with EB receiving quality of life, alongside our objective measurements. As controls, and locationofblistersalongwiththeaffect thatthisishavingon frequency size, in alterations on data subjective collating are we res. These questionnaires continue to be completed monthly, and development of blisters on their feet, activity levels and the pain sco about questionnaire tailored a in filled subjects issued, was footwear new the time the at analyses, pressure the with Along repeated in their newly issued and fitted rocker bottom footwear. plantar pressuremeasurementsystem. The measurementswere anin-shoe using takenintheircurrentfootwear dynamic gaitwere presentation. Eachrecruit’s plantarpressuremeasurementsduring ported regularplantarblisteringformationaspartoftheirclinical (6 males and 3 females, ages ranging from 18-75yrs old) that re methods: velopment ofplantarblisteringinpatientswithEB.Materials& been consideredaspartofanytreatmentplaninreducingthede we areaware,theeffect ofthealteredfootbiomechanicshasnot as far as However, pathologies. musculoskeletal limb lower of of foot. They havebeenusedasatreatmentmodalityforvariety through these areas and spread force more evenly across the sole Rocker bottomfootwearisbelievedtoreducethepeakpressures sure which, in combination with EB, results in regular blistering. cycle. However, these areas are exposed to peaks in plantar pres of thefootwhichasactpivotstoaidpropulsionduringgait the bigtoes. These areasareknownasthethreenaturalrockers areas are typically the heels, metatarsal heads (balls of the feet) and due tonaturalfootbiomechanicsandtheirresultantforces. These intypicalareas plantarblistering with tendtopresent (EB) simplex Introduction &objectives:PatientswithEpidermolysisBullosa National EB Adult Service–UBHSolihull Mark O’Sullivan,LisaJames, Adrian Heagerty, NatashaHarper SIMPLEX; A PILOT STUDY PATIENTS WITH EPIDERMOLYSIS BULLOSA DEVELOPMENT OF PLANTAR BLISTERSIN ON FOOT BIOMECHANICS AND THE THE EFFECT OF ROCKERBOTTOM FOOTWEAR P93 64 EB2020 1 Epidermolysis bullosaisadevastatingdiseaserelatively The authors selected 9 suitable patients with EB simplex The authorsselected 9suitable patientswith EBsimplex st WorldCongressonEpidermolysisBullosa The comparison The comparison ------Brazil 1 Mendes, Luciana EPIDERMOLYSIS BULLOSA:CASEREPORT P95 develop sepsis due to the loss of the stratum corneum barrier, corneum stratum the of loss the to due sepsis develop such asmalnutritionandanemia. EBpatientsaremorelikelyto nary tract, musculoskeletal system, as well as metabolic disorders eyes, nose, oral mucosa, dentition, gastrointestinal and genitouri on thelivesofpatientsandtheir families. The diseasemayaffect is averyraredermatologicaldisorder andithasagreatimpact which isduetothedevelopmentofcarcinoma.Conclusions:EB “wounded”. They also present the severe evolution of the disease, from prejudice and non-insertion in socialization, they are called similar, suffer more is they difficulty stay.the hospital adults, In delivery canleadstonewbornsworseningtheirinjuriesandlong birth injuries. The routineproceduresthatareperformedafter severe suffers already baby the natural, or surgical delivery: of disease isnotdiagnosedbyultrasound.Dependingonthetype the as professionals, maternity to problem major a presents NB the with conduct diets. The and dressings as such care, adequate of lack the all, by faced challenge main the be to proved disease family. and mothers of reports manual, care of use analysis, records cal medi visits, home through 2018, and August February between conducted report, case descriptive and observational an is This patients both with EpidermolysisBullosafor6months.Materials&methods: adults, two and (RN) newborn one child, one in Objective: Reportthecareofhealthteamandfamilymembers extremely importantasitavoidsfurtherstressforEBpatients. for specialatraumaticandeasy-to-removepain-freecoversis repercussions and impacts on patients’ quality of life; the need and dystrophicbullousepidermolysis.Injurieshaveconsiderable the bubble². They fall into three main groups: Simple, junctional to rise giving fluid, protein-rich or whey with filled is layers the between formed space the Thus, easily³. separate skin of layers various effectively, the work so not do fibers bonding these In EB, fibers. protein collagen by together linked layers several of nifestation istheformationofepithelialblisters. The skin consists mucosa. Itisagroupofhereditarydiseaseswhosecommonma and congenitaldiseasecharacterizedbyfragilityoftheskin Introduction &objectives:EpidermolysisBullosa(EB)isarare 2 best possible medical care, both to our patients and their families. As health- care providers, we have a responsibility to provide the result ineducationandtrainingofhealthpersonnelatalllevels. desolating condition.Casessuchastheonewepresenthereshould and tohelpboththepatientstheirparentsdealwithsucha prognosis, lethal its and disease the about possible as honestly prompt and correct diagnosis is paramount to inform them as of thefeelinguncertaintywhendealingwiththisdisease. A earlier andbettersupportivecare.EBparentsusuallycomplain the referral of the patient to a specialized EB centre, allowing for expedited have would diagnosis earlier an However, outcome. final the alter not did probably diagnosis initial wrong the here, is ultimately fatal, even with the best of care. In the case we present course of the disease and have received genetic counselling. HJEB Patient’s parentsrequiredpsychologicalsupportallthroughthe failure duetoseveresepsiscausedbyPseudomonasaeruginosa. died attheageof3monthsbecausecardiacandrespiratory and haematological disorders, and recurrent infections. The child gastrostomy due to diminished ingestion), severe hydroelectrolytic of thepharyngealmucosa(whichrequiredperformancea erosions painful area, surface body total 60% involved which laminin 332. The babypresentedextensivehemorraghiclesions after antigen mapping ofaskinbiopsyshowed a completelack of Dermatology Nurse, Clinical Manager, Mölnlycke WOCN Nurse,SalesManager, Mölnlycke Results: The managementwiththelesionscausedby 1 , Santos,Paloma 2 , Araújo José , Araújo ® HealthCare Brazil, 3

® Health Care - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV 1 containing information about the disease, non-adherent dressings, riod iscrucialforagoodevolution ofthedisease. To provideakit professionals incharge. Adequate initialcareintheneonatal pe Bullosa (EB)isadramaticmoment forthefamilyandteamof Introduction &objectives: The birthofachildwithEpidermolysis Mehl Magno¹, A. J. A. EPIDERMOLYSIS BULLOSA SUPPORT TONEWBORN WITH THE BUTTERFLY KIT -CLINICAL AND LOGISTIC P97 tures inindividualswithEB. effective wayoftreatingdysphagiacausedbyoesophagealstric fluoroscopically-guided oesophageal dilatation is a safe and very major complicationsoverthestudyperiod.Conclusions:Repeat score was 0.44 with a mean improvement of 1.52. There were no dysphagia scorewas1.96. The meanpostproceduredysphagia Collectively,5). (median patient per pre-procedure 9.3 mean the 276 ODswithinthestudyperiodwithameannumberof of total a had RDEB with Patients months. 10 was collectively study period. The medianintervalbetweenODsfor all patients the during performed were ODs 325 total, In study. this in ded patients and finally 4 patients with Kindler syndrome were inclu (DDEB) bullosa epidermolysis dystrophic dominant 6 patients, Twenty-five recessive dystrophic epidermolysis bullosa (RDEB) dilatations. Statistical analysis was done using excel. Results: and majorcomplications. We alsorecordedtheintervalbetween of thestudywereimprovementinclinicaldysphagiascore 4 (unabletoswallowliquidsorsolids). The primaryendpoints wards and were measured on a scale from 0 (normal swallow) to on 2017 from available were scores Dysphagia recorded. also were included.Dysphagiascorespre-andpost-procedure centre for adults with EB. All dilatations between 2005 and 2019 reference single a at OD fluoroscopically-guided undergoing a retrospectivereviewofthemedicalrecords35EBpatients the dysphagia score (DS). Epidermolysis Bullosa(EB)patientcohortbyimprovementin an of (OD) dilatation oesophageal fluoroscopically-guided of assess the clinical benefit and immediate and long-term outcomes as welllimitingsocialactivities. The aimofthisstudywasto growth and healing wound deficits, nutritional exacerbating but effect onapatient’s qualityoflifeaffecting notonlytheirswallow profound dysphagia. a associated has and This stenosis scarring, In briefthereisblisteringoftheoesophagealtractandsubsequent (DEB), in particular, is associated with oesophageal complications. skin andmucousmembranes.DystrophicEpidermolysisBullosa of raregeneticskinconditionscharacterisedbyfragilitythe Introduction &objectives:Epidermolysisbullosa(EB)isagroup Guy’s andStThomas’ NHSFoundationTrust McGrath, J.E.Mellerio, A. Diamantopoulos C.A. Drislane,N.Thulasidasan,J.Clapham,D.T Greenblatt, J.A. DILATATION INEPIDERMOLYSIS BULLOSA FLUOROSCOPICALLY-GUIDED OESOPHAGEAL SYMPTOMATIC BENEFIT OF P96 patient toamputationandlife-threatening. the leading sites, primary multiple be may there and lesions, nic cell carcinomacanalsooccurinthesepatientssiteswithchro facilitating microbialpenetration. The developmentofsquamous nic Wounds, Technologies for the Prevention and Treatment of Acute and Chro- of BlumenauandNursingCoordinator ofDebra Brazil Brazil, versity FoundationofBlumenauandMedicalDirector of DEBRA Pediatric Dermatologist, Teacher attheFURB-Regional Uni- 2 Medical Consultant, Teacher andResearcher onNew 3 Nurse at theFURB-Regional UniversityFoundation Nurse 2 , K.A.Osti Materials & methods: 3 We undertook - - - - - able togivenewbornsahigherqualityoflifeandlowermortality. increased confidence in the volunteer team and with this we were as well as bullosa, Epidermolysis with newborns of notification KIT project, there was greater dissemination of EB and increased Butterfly Little the Withof lifebabieswithEB.Conclusions: became thesymbolofinstitutionandbattleforquality since has KIT butterfly little The life. of quality baby’s the sing pain andpreventingcomplicationsfuturesequelaeincrea initiative that minimizes the occurrence of new injuries, reducing and specialdressingsneededforin-hospitalcare. An important teams withtechnicalsupportforpropermanagementofthenewborn healthcare provide we notified, is birth the Once KIT”. butterfly “little named was it and 2018, January on launched was project care products and support at the time of the neonatal period. This wound proper information, bring volunteers of team a dressings, difficulty of quick access to primary care of babies, such as special the with coupled professionals, neonatal most to unknown is EB where births, live cases/million 19 of incidence an country,with treatment ofEBleadstoworseningthecondition.Inacontinental cations andtheuseofconventionalproductsforotherdiseasesin alone. Professional’s lack of knowledge about the disease, compli which makesitimpossibleforanaveragefamilytobearthecosts costs, high also having families, their and patient the sufferingto Epidermolysis bullosaisarareincurablediseasethatcausesintense the affection and concern of the team with the newborn. symbolizes that doll butterfly a and language simplified a in tion prevalence of Candida albicans (69.8% vs. 9,1% in controls), Stap of 12).Oralmicrobiotaanalysisat initialexaminationshowedhigh protocol (among21ofthesepatients 9werecariesfreeattheage DEB butonlyunderthecondition ofstrictadhesiontoprevention diseases prevention program proved to be efficient in children with of teeth-retainedprosthodontic and orthodonticappliances.Oral use and extractions teeth care, dental of types all after seen were pletely oneweekaftertheprocedures.Nolong-termcomplications pediatric crownsplacemenonmolars. The lesionsresolvedcom children immediately after local anesthesia, teeth extractions and 5 severemicrostomiacases.Bullasanderosionswereseeninall cing challengingimpressiontaking)andsplintsmanufacturingin (repla usedforintraoralscanning was system splints. CAD/CAM successfully treatedbyconsecutivesequencesoforthodontic were crowding tooth extreme with children 10 crowns, separate with treatment prosthodontic received adolescents 8 anesthesia, preventive programs.Results: diseases oral of efficacy the reveal to intervals 6-months two in in DEBpatientsaswell22healthyaged-matchedcontrols after. Oral wound and mucosa microbiota were also inoculated assessed immediately after the procedures, 1 week and 6 months oral rehabilitation in 2013-2018. Soft tissues complication rate was comprised 86childrenwithDEBaged2-18yearswhoreceived epidermolysis bullosa(DEB).Materials&methods:Thestudy sthodontic andorthodontictreatmentinchildrenwithdystrophic feasibility of dental diseases prevention program, dental care, pro Introduction &objectives: The aim ofthestudywastoevaluate Moscow, Russia Central Research InstitueofDentistryandMaxillofacial Surgery, Dmitrieva M. Korolenkova, A. Poberezhnaya, N.Starikova, N. Udalova, BULLOSA CHILDREN WITH DYSTROPHICEPIDERMOLYSIS COMPLEX DENTAL REHABILITATION IN P98 Along with the supplies, it is also included infographics, informa kit whichisbeingsponsoredbythemajorwoundcarecompanies. dressing non-adherent 3-month a organized have we Consensus, Wound International 2017 the on Materials &methods:Based support. family as well as teams, health to support medical and Oral rehabilitationundergeneral Acta DermVenereol Suppl220 Posters Results: Results: 65 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta 1 Table 1.Overview ofDEBPatientsBiopsiedforRenalDysfunction mine ifourresultsaregeneralizable tothelarger EBpopulation. this caseseries.Futurelarger cohortstudiesareneededtodeter in three therapy,did antibiotic as with outcomes renal improved infections as causative of GN is unclear. Such patients may have EB patientswithrenaldysfunction. The role of priorStreptococcal may beapotentiallyunrecognizedcauseofglomerulonephritisin glomerulonephritis (GN)withmesangialC3deposition.GN dystrophic EBandrenaldysfunctionwhowereallfoundtohave with patients five describes it that in unique is series case This resolution ofproteinuriaand AKI intwopatients.Conclusions: significant improvement in renal dysfunction, including complete treated withantibioticshadmildto patients 3 The mycophenolate. and steroids with treated was patient one and (ACEI), inhibitor was treated with steroids and an angiotensin-converting enzyme patient one antibiotics, with empirically treated were patients neous Streptococcal infections and one had pyelonephritis. Three 2 patients.Fourofthepatientshadpreviouslydocumentedcuta inflammation was found in four patients and interstitial fibrosis in sangial or para-mesangial regions. In addition, tubulointerstitial deposits located in the sub-endothelial, sub-epithelial and/or me intense mesangialstainingforC3.Electronmicroscopyrevealed proliferationwith mesangial increase showed logy forallpatients Onepatientunderwentrepeatbiopsy.18 years. Renalhistopatho times baseline). Patient ages at time of biopsy ranged from 10 to 1.5 or mg/dL 0.3 least at by creatinine serum in increase an be per KidneyDiseaseImprovingGlobalOutcomesguidelinesto of hematuria,proteinuriaandacutekidneyinjury(AKI,defined lowed atourinstitutionunderwentrenalbiopsiesforindications fol currently DEB with female) 2 male, (3 patients five 2019, - tion whounderwentrenalbiopsy. Results: Retrospective chart review ofEB patients followed at ourinstitu biopsy forglomerulonephritis(GN).MaterialsandMethods: at ourinstitutionfordystrophicEB(DEB)whounderwentrenal hology, treatment and clinical outcomes of five patients followed renal dysfunction. This caseseriesdescribes therenalhistopat known unifyingetiologyoroptimaltreatmentforEB-associated no is there Currently dialysis. for need the as such morbidity, molysis bullosa (EB) may have renal glomerular disease causing Introduction and Objectives : Patients with severe forms of epider 2 Erica Hughley, MD CASES EPIDERMOLYSIS BULLOSA: A REPORT OF FIVE C3 GLOMERULONEPHRITISINDYSTROPHIC P99 compromised localimmunityintheoralcavity. pathogenic microbiotainDEBpatientsisprobablyaresultofthe techniques anduseofCAD/CAMsystem.Higherprevalence options werefeasibleinDEBchildrenduetosofttissuessparring treatment orthodontic and prosthodontic care, dental routine All seen atthesecond6-monthintervalexamination.Conclusions: oral diseasespreventionprogrameliminationofthegermswas receiving cases DEB of 42,2% In patients. DEB in colonization 59.1%) vs (97.5% mutans Streptococcus and 22,7%) vs. (84.1% hylococcus aureus (60.5% vs. 9,1 in controls), Rhotia dentocariosa 66 Edward Nehus,MD cinnati, OH Dermatology, Cincinnati Children’s HospitalMedical Center, Cin- trics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH EB Type Sex Patient n# Cincinnati Children’s Epidermolysis Bullosa Center, Division of Division of Nephrology and Hypertension,DepartmentofPedia EB2020 1 1 DDEB* Male st WorldCongressonEpidermolysisBullosa 1 1 ; Anne WLucky, MD 2 RDEB-GS Male 3 RDEB-GS Male 2 4 RDEB-GS Female ; Bret; Augsburger Between years 2015 years Between 5 RDEB-GS Female 2 and ------

la Youssefian Research Institute, ShahidBeheshtiUniversity, G.C.,Tehran, Iran cal Sciences,Tehran, Iran, 1 Reza Shakouri EPIDERMOLYSIS BULLOSA PATIENTS FOR THETREATMENTLASER OF IN WOUNDS PHERIC PRESSUREPLASMA LOWVERSUS LEVEL THE EFFICACY SAFETYAND OF COLD ATMOS­ P100 wound healinginthesepatients. sizes areneededtoclarifythe mechanism ofplasmaeffects in this very challenging disease. Further studies with more sample can beconsideredavaluablemodality forthewoundhealingin atmospheric pressureplasmais as effective aslowlevellaserand Vaseline gauze. Conclusions: The study results suggested that cold and alsothetimetohealwaslesscomparedwiththatoflaseror the plasmawasmoresuccessfultoreducepainrapidly size ofthewoundscomparedto Vaseline gauze(p Although both laser and plasma methods reduced significantly the laser groupcompletelyhealedinthe8thsessionoftreatment. (90.90%) wounds in plasma and all wounds (12/12; 100%) in the One out of 6 (16.66%) wounds in the control group, 10 out of 11 ment, 4 and 12 weeks after the last session of treatment. weeks) andthewoundswereevaluatedineachsessionoftreat 8 average (or improvement complete until week a twice control, 2 wounds withlaserandonewasdressed Vaselineplasma, gauzeasthe with treated randomly were wounds 2 patient, each with noresponsetostandardtreatments)wererecruitedandin to previous therapies (wound that persists more than 3 months Materials &methods:SixEBpatientswhohadfailedtorespond wound carewith Vaseline gauzeforthetreatmentofEBwounds. atmospheric pressureplasmaversuslowlevellaserorstandard cold of safety and efficacy the compare to aimed study,we this of coldatmosphericpressureplasmaonthewoundhealing.In interaction. Recently, studies have focused on the potential effects medicine and dermatology may beaspecial tissue-reactive species bial, tissue stimulation, and other therapeutic effects of plasma in important contributing factors to the anti-inflammatory, antimicro produce heatandreactiveoxygennitrogenspecies.Oneofthe can and fields electric and radiation ultraviolet of kinds several emits and atoms ionized of matter,composed the of state the fourth is Plasma ulcers. heal to difficult of treatment the for used laser andrecentlycoldatmosphericpressureplasmahavebeen level Low dressings. specific and therapy cell including healing treatment, there are a number of modalities which can help wound mucocutaneous bullae and erosions. In the absence of a definitive tic inheriteddiseasecharacterizedbyskinfragilityandchronic Introduction &objectives:Epidermolysisbullosa(EB)isagene DDEB, dominantdystrophicEB;RDEB-GS,recessiveEB-generalizedsevere *genetic work-upforCOL7A1mutationspending. son University, Philadelphia, Pennsylvania, USA, taneous Biology, Sidney Kimmel Medical College, Thomas Jeffer Iran, Treatment nosis Renal Diag logy Outcome Clinical Histopatho (years) Age atBiopsy Renal Biopsy Indication for Physics Department of Shahid Beheshti University, G.C.,Tehran, 2 Skin Research Center, ShahidBeheshti UniversityofMedi- - - Steroids, ACEI IgA nephropathy deposits sub-endothelial for C3&IgA; Mesangial staining change No longterm 18 - Proteinuria AKI hematuria - Microscopic 3 , HassanVahidnezhad 1 , Fahimeh Abdollahimajd , Antibiotics C3 GN for C3 staining Mesangial resolved AKI proteinuria, Improved 17 - AKI - Proteinuria hematuria - Gross 3 Department ofDermatologyandCu- Steroids, Mycoph C3 GN deposits and para-mesangial for C3;mesangial Mesangial staining Unknown enolate 10 - AKI - Proteinuria 3 , JouniUitto - 2 *, ShirinSamsavar C3 GN deposits C3; mesangial staining for Mesangial proteinuria hematuria and Resolved AKI, Antibiotics 14 - AKI - Proteinuria hematuria - Gross 3 , BabakShokri 4 Laser -Plasma GN Mesangial proliferative mesangial deposits sub-epithelial para- for C3;mesangialand Mesangial staining Improved AKI ACEI/Antibiotics 14 /15 - AKI - Proteinuria - Grosshematuria < Results: 0.001), 1 , Lei- 1 , - - - - 4 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV We intend todisclosethenationalregisterofEpidermolysisBul statistics andthereisaneedtocreatemethodsincreasetheir. literature. stable, 1.77 remained cases/10.000.000, which is has lower than the years cases in the 2 world last the in incidence The release. literature, although it has increased in recent years after new data in 2018 was 3.26/1,000,000 population and is lower than the world the predominantformandmaincauseofdeath. The prevalence bullosawas epidermolysis dystrophic genders.Recessive between cases was 883, with 113 deaths. There was no significant difference and the age at which they wereperformed. years (2004-2018). We analyzed the surgical procedures performed Department of Paediatric Surgery at our institution in the last 15 a retrospectivestudyinpatients withEBwhoweretreatedbythe in ourmultidisciplinaryunit.Materials&methods: surgeons intheintegralmanagementofpatientswithEBtreated was todescribeandanalyzetherelevanceofspecializedpaediatric plex disease which requiresamultidisciplinary approach; ouraim Introduction &objectives:Epidermolysisbullosa(EB)isacom Gutiérrez Muñoz-Serrano, Nuria Leal, Paloma Triana, Juan Carlos López- Carlos Delgado-Miguel, Miriam Miguel-Ferrero, Antonio J. EPIDERMOLYSIS BULLOSA THE ROLE OF PAEDIATRIC SURGEONSIN EB PATIENTSSURGEONS: NEEDEBSPECIALIZED P102 the publicpolicesandstimulatingresearchonEBinourcountry. losa andpublishthestatisticstouseasasourceforplanning 5% (α of level significance a and package statistical PRISM® HPAD men orwomen.StatisticalanalyzeswereperformedwithGRAP Fisher’s exacttestassessedtheproportion ofpatientsbetween genders. differencebetween the tested we test, chi-square Using gender andagetestedfornormalitybytheShapiro-Wilk test. absolute frequenciesandpercentages.Patientswereseparatedby were described according to the average and standard deviations or ces. We useddescriptivestatisticsfordataanalysis. The variables social networks, support groups and dermatological medical servi April 2019. We searched for patients in regional associations, on EB registry, from DEBRA website, was analysed January 2014 to global literature.Materials&methods:Thedatafromthenational is todeterminetheepidemiologicaldataandcompareitwith and givepatientsaccesstonewtreatments. The aimofthisstudy and a single database, we will be able to discuss public care policies the treatment. With an approximate numberof cases in the country Epidermolysis BullosaResearch Association (DEBRA)isunifying publications containingthenumberofpatients. The Dystrophic haven’t calculated.InBrazilwe theincidenceis from which found Countries such as the USA and Scotland have official EB records, data iscollectedinsupportgroupsanddermatologycarecenters. Only fewcountrieshaveadequateepidemiologicaldata. This patients. of number the knowing with along needed, public are policies and development treatment, right the to access have to involves amultidisciplinaryteamanditisexpensive.Foreveryone rare disease affecting 11 people per million inhabitants. Treatment Introduction & objectives: Hereditary Epidermolysis Bullosa is a 2 J.A. Magno¹,M.M.Frant OVERCOME NATIONAL REGISTER- A CHALLENGE TO BE P101 UFPR andTeacher attheFederalUniversityofParaná(UFPR) dinator ofthe Specialization Course inPediatric Dermatology at 1 Foundation of Blumenau andMedical Director of DEBRA Brazil, Student of Medicine inPositivo University, Pediatric Dermatologist, Teacher at the Regional University = 0.05) was considered. Conclusions: The notifications are below the worldwide 2 , V.O. Carvalho Results: The numberofregistered 3 3 Carvalho V.O. Coor Results: We performed Fifty-seven - - - - - EB and2junctionalEB.Sixty-oneinterventionstoreleasepseu simplex 2 EB, dystrophic recessive presented them of Fifty-five patients (28male;29female)underwent263surgical procedures. in total(meanof3.9 with a median of 10.5 months, requiring 43 subsequent excisions excised with free margins. In were 11 of tumors them, the carcinoma relapsed, patients, 14 all In biopsy. pre-excisional required with ameanageatdiagnosisof22.4 patients developed squamous cell carcinoma (11 male; 3 female), per patient, allowing for recovery of regular oral intake. Fourteen colostomy (2 patients), port-a-cath placement (1 patient) and ap patients), (2 retractions skin of release patients), (3 circumcision were: partial skin grafting on benign chronic wounds (5 patients), limb amputation in 9patients. Other less frequent procedures Results: assessments, change in iscorEB-p score over time was analyzed. score was determined by ANOVA, and in patients with 2 or more patients with RDEB, the relationship of decade of age to iscorEB-p stratified by EB type/subtype (EBS, JEB, DDEB, RDEB). Within The primaryoutcomesareiscorEB-p compositeandsub-scores Patients completediscorEB-pwhenpresentingforroutinecare. Database(EBCCOD). EB ClinicalCharacterizationandOutcomes EB centersintheUnitedStatesandCanadacontributingdatato syn EB: with patients of management the in role relevant very pendectomy (1patient).Conclusions:Paediatricsurgeons play a 7.9 of age mean a with patients, 37 in performed were endoscopy) percutaneously,by (placed guided Gastrostomies life. of quality limb. Most patients (87.7%) referred the procedure improved their hand, 4 on both hands simultaneously and only one on the lower dosyndactyly were performed: 34 on the right hand, 22 on the left hods: patients with repeated assessments over time. to iscorEB-p score; and 3) discern trends in iscorEB-p scores in ferent types/subtypesofEB;2)evaluatetherelationshipage range ofiscorEB-pscoresandsub-scoresinpatientswithdif leisurely activities. The goalsofthisstudyareto1)describethe and daily on effect and mood sleep, limitations, functional itch, sections; the patient-reported section (iscorEB-p) measures pain, (iscorEB) includesbothclinician-assessedandpatient-reported Scoring Clinical Outcomes ofResearch forEpidermolysis Bullosa for Instrument The lacking. are setting, real-world a in ticularly par time, over and types/subtypes EB across outcomes reported understood, larger scale studies that systematically assess patient- of epidermolysisbullosa(EB)onpatients’ qualityoflifeare Introduction &objectives: Although thesymptomsandimpact ronto, ON,Canada Children’s Hospital Colorado, Aurora, COUSA andSick Kids, To- sortium Elena Pope;andtheEBClinical ResearchLara-Corrales; Con- Anna L.Bruckner;James A. Feinstein; Kathleen Peoples; Irene EPIDERMOLYSIS BULLOSA PATIENT-REPORTED OUTCOMESIN A MULTICENTER COHORT STUDY EVALUATING P103 specialized paediatricsurgeons intheirstaff. benefit from the existence of multidisciplinary unitswhich include malignant tumorsdecreasemorbidityandmortality. EBpatients the qualityoflifethesepatients;earlybiopsyandexcision improve dilations esophageal and gastrostomies release, dactyly was performed on 68 occasions, with a mean of 3.1 impeded normal oral feeding. Endoscopic esophagealdilatation which EB, of course the during stenosis esophageal presented Twenty-twopatients 16years. of time median a after them, of 5 nutritional status, allowing for subsequent gastrostomy closure in ± 4.7 years. All patientspresentedamajorimprovementintheir Longitudinal, repeated measures cohort study conducted at 253 patientsfromtheEBCCOD had1ormoreiscorEB- ± 3.1 surgeries per patient), which involved which patient), per surgeries 3.1 Acta DermVenereol Suppl220 ± 5.5 years. Twelve patients Materials & met Posters ± 2.1 dilations 67 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Diseases, Groningen, theNetherlands population. per millionlivebirthsandprevalenceratescalculated curate diagnosticsandfollow-up.Incidencerateswerecalculated Netherlands. Netherlands. Epidemiological figureswere calculated based on ac calculate accurateincidenceandprevalenceratesforEBinthe referred byspecialistsfromforeigncountrieswereexcludedto EB with Patients included. were Netherlands, the in based and 2018, to 1988 from register EB Dutch the in registered EB with patients all study, cross-sectional this Materials &methods:In years. 31 past the over established Netherlands, the Groningen, cohort oftheDutchExpertiseCenterforBlisteringDiseasesin EB- well-characterized the from extracted EB, of subtype each for data epidemiological valuable present we Here, essential. is tive trial outcomes, recognition of well-characterized EB-cohorts translated intotherapeutictrials. To ensurevalidandrepresenta being currently are which EB, for cure a finding towards made are advances scientific Significant Introduction &objectives: Department of Dermatology University ofGroningen, UniversityMedicalCentre Groningen, R. Baardman NETHERLANDS IN THE EPIDEMIOLOGY OF EPIDERMOLYSIS BULLOSA P104 and detectschangesinthoseoutcomesovertime. be usedtoassesspatient-reportedoutcomesintheclinicalsetting iscorEB was designed to be used in clinical trials, iscorEB-p can patients with RDEB, disease impact correlates with age. Although JEB are more impacted than patients with EBS or DDEB, and in and urinary problems). Conclusions: Patients with RDEB and problems with bowel movement), but not others (itching, eye pain, pain, bonehandissues,problemswitheatinganddrinking, increases in scores were observedacross some symptoms (overall Among RDEB patients who had 2 or more iscorEB-p assessments, 20-29yo: 38.4; 34.6, 10-19yo: 29.9, (1-9yo: patients RDEB for category age sub-scores differed atbaseline.Baselinetotalscoresdiffered by 95%CI 18.5-24.5), and DDEB (15.6; 95%CI 11.0-20.1). Domain 31.0-36.9), followed by JEB (29.7; 95%CI 21.3-38.1), EBS (21.5; baseline total scores were highest in RDEB patients (34.0; 95%CI with interval spacing of measurements 0.7-1.2 years 2 depending on had EB subtype. Mean patients of 45% (50%). female and (78%), white (53%), <10yo were patients Most RDEB. 48.2% and DDEB, 14.6% JEB, 7.6% EBS, had 29.6% assessments. p 68 mooij clinically and molecularly well-characterized EB-cohort provides intermediate] and 8.1 years for recessive EBS. RDEB-generalized severeand 7.1 yearsforRDEB-generalized for years [17.6 RDEB for years 14.6 intermediate, generalized 2.9 monthsforJEB-generalized severeand43.8yearsforJEB- of EB-related complications was 5.5 days for JEB-pyloric atresia, DEB and7EBS). The medianageofdeathforpatientswhodied 16 JEB, (47 EB of subtype recessive a having patients 70 which of died, had EB-cohort Dutch our in EB with patients the of 77 0.5 and 0.2 [KS], respectively. During the investigated time-period, 21.1 and 13.3 [EBS], 9.3 and 2.1 [JEB], 14.2 and 8.3 [DEB] and incidence andprevalenceratesforeachmajorsubtypeofEBwere The genes. different 17 in respectively,ormutations families] with patients [4 0.8% and families)] (103 patients [161 32.9% families)], (72 patients [87 17.8% families)], (132 patients [238 EB (DEB) and Kindler syndrome (KS) were diagnosed in 48.6% dystrophic (JEB), EB junctional (EBS), simplex EB population. rate forEBintheNetherlandswascalculatedtobe23.9permillion an incidencerateof45.1permillionlivebirths. The prevalence average annual number of newborn patients with EB was 9, with The 2018. and 1988 between Netherlands the in identified were 1 , M.F. Jonkman EB2020 1 Results: 1 *, V.K. Yenamandra p = st WorldCongressonEpidermolysisBullosa 0.02), but not significantly for other subtypes. Overall, 490 patients (311 families) with EB 1 , P.C. vanden Akker 1 andGenetics 1 , J.C. Duipmans 1,2 2 ,Centre forBlistering , M.C.Bolling Conclusions: Our 1 , A.M.G. Pas- , A.M.G. 1 - - Mellerio 1 Birmingham, Solihull,UnitedKingdom ted Kingdom, tology, Guy’s and StThomas’ NHSFoundationTrust, London,Uni- during day 180. tion was observed at day 60. There were no severe adverse events (1–3 × 10^6 cells received threeintravenous infusions of allogeneic UCB-MSCs 2 children) were included in this clinical trial. Each participant Materials &methods:SixKoreanRDEBpatients(4adultsand efficacy of systemicallogeneicUCB-MSCstherapyforRDEBpatients. clinical possible and safety the determine to is study stem cells correct RDEB murine model. The objective of this of humanumbilicalcordblood(UCB)-derivednonhematopoietic Recent preclinicalstudydemonstratedthatasystemicinfusion (MSCs) have shown therapeutic potential for RDEB patients. after minor trauma. Bone marrow–mesenchymal stromal cells in COL7A1 and characterized bymucocutaneous blistering Bullosa (RDEB) is a severe genodermatosis caused by mutations Introduction &objectives:RecessiveDystrophicEpidermolysis Seung JuLee PATIENTSRDEB WITH ALLOGENEIC UCB-MSCS THERAPY FOR SAFETY AND CLINICAL EFFECTSOF SYSTEMIC P105 localised (EBS-LOC) (EBS): simplex EB with 1056 were There 96%: in recorded diagnosis with patients, living 2141 were there 23/09/2019 on tunity forepidemiologicalstudy. Results: born since 1922 have been registered, providing a unique oppor losa (EB)servicewassetupintheUK. To date2345individuals Introduction &objectives: In 2002 a national Epidermolysis Bul Gabriela Petrof FROM THE NATIONAL DATABASE THE EPIDEMIOLOGY OF EBIN THE UK:DATA P106 in furtherclinicaltrials. confirmed be to benefits, clinical possible of indications provide tion ofallogeneicUCB-MSCsinpatientswithRDEBissafeand with muscular dystrophy (EBS-MD) (EBS-GS/GI) 1 Pharmaceutical, Co., Ltd, Hospital, Birmingham,UnitedKingdom, partment ofDermatology, BirminghamWomen’s andChildren’s Soo-Chan Kim Kangstem BiotechCo.,Ltd cine, Seoul, Korea, Children NHS Foundation Trust, London,United Kingdom, markedly reduced at day 60. No significant increase in C7 deposi in the patient’s skin at baseline, but the number of both cells were increased numberofc-kit+mastcellsandCD68+macrophages 43% and 13% at day 60 compared to baseline. We also found the to baseline.Painandpruritusscore(VAS) werealsoreducedby body surface area (%) were reduced by 50% at day 60 compared (-15 point) from reduced baseline to day significantly 60. Blister was count and blister (%) area/ area surface body total BEBSS Bullosa Severity Score (BEBSS) was -16 point at 60 days. Mean in meandiseaseseveritymeasuredbyBirminghamEpidermolysis Netherlands. the needforcareanddiseaseburdenpatientswithEBin demonstrates data this Additionally,trials. upcoming of design accurate epidemiologicaldataforEBthatisinvaluablethe Department of Dermatology, Yonsei University College of Medi- Department ofDermatology, GreatStreet Ormond Hospitalfor 3 , MariaPapanikolaou 1 4 = , KinamKim 1 Department ofDermatology,UniversityHospitals , SangEunLee 1 153, with mottled pigmentation (EBS-MP) pigmentation mottled with 153, Conclusions: thatadministra The resultssuggest , MalobiOgboli kg–1) with no HLA matching. = 2 Cellular Therapeutics Team, Daewoong 690, generalised severe and intermediate 3 Department ofClinical Development, 2 , BoyoungCho 1 3 , Adrian Heagerty , Adrian 2 , Anna E.Martinez = 13, not otherwise specified 3 Department ofDerma- Regarding prevalence, 2 , KyounghwanRoh Results: 4 ,CeliaMoss 1 , JemimaE. Change = 2 De- 35, 2 3 - - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV ethnographic factorsandmorecompleteascertainment. The mo reflecting possibly Australia, and USA the from reported those GS) (JEB- severe generalised (JEB): EB junctional had Seventy-two atresia (JEB-PA) PhD 1 versity SchoolofMedicine, Boston, MA,USA, were examined per eye, scores were averaged and compared bet was made using a standardized scoring scale of 0-3. Five sections corneal features known to be potentially abnormalinthis model 10 of Grading pathologist. ocular an by performed was mice) (8 eyes 16 of staining H&E with Histology published). (previously (ethical endpoint). Corneal opacities were graded on a scale of 0-4 a weeks using Topcon20 until 8 from slit-lamp, enabled camera status. Twenty micewere examinedandphotographedweekly homozygous confirm to mice all on performed was Genotyping hydrogel. and 76A, diet-gel bedding, fiber cellulose including 36 months.Specialprecautionsweretakentopromotesurvival over recorded were mice hypomorphic deficient VII collagen of mination oftheseanimals.Materials&methods:Survivalrates disease, and lessons learned from 36 months of breeding and exa ophthalmic of course natural the report we Herein, seen. be can of ocularinvolvement,andsurvivaltoanagethatdisease morphic mouse model has unique challenges, including asymmetry Introduction & objectives: Ophthalmic study of the DEB hypo Vicki M. Chen,MD AND SURVIVAL MOUSE MODEL:CHALLENGESOF ASYMMETRY UNDERSTANDING OCULARDISEASE IN THE DEB P107 and geneticcounsellingoverthelast20years. reduction in birth incidence for severe types may reflect better care dest increase in survival time of babies with JEB-GS, and possible babies with JEB-GS (p respectively. There isasuggestionofincreasedsurvivalforUK 15% and 28% 47%, 70%, were JEB-GS in months 18 and 12 6, 3, at rates Survival 2010). Dermatol, Arch al, et Kho - months (5.8 months - Yuen et al, Br J Dermatol, 2011) and Australia (6.8 Netherlands the 2010), Clin, Dermatol al, et Laimer - months (5 in Austria reported than higher months, 8 of mean with 60-300) (IQR days 150 was death of age median UK the years, 19 aged 1 with JEB-GI. Regarding JEB-GS, excluding 1 surviving outlier with JEB-PA, 11 with RDEB, 4 with EBS-GS, 1 with EB-NOS and 20-year birth-cohort 117 died before age 16y, 76 with JEB-GS, 8 births andRDEB-GSfrom6.8to2.9/millionlivebirths.Inthis reductions inbirthratesforJEB-GSfrom9to3.8/millionlive lier (2002-2010) and later (2011-2019) birth cohorts, we observed recessive (RDEB) (EBS-NOS) DVM sity, Palo Alto, CA population are EBS with Kindlersyndromeand36EB-NOS.Prevalences/million EBS-GS EBS: with 515 were There EB. with newborns 1209 registered Regarding incidence, during the 20 year period to 23/09/2019 we were 129 with JEB: JEB-GS EBS EBS the following incidence rates/million live births/year: all EB (51). syndrome gives skin This peeling acral and (50) ichthyosis Forty-seven hadEB-relatedconditionsincludingepidermolytic DEB-NOS LOC Tufts Medical Center, Floating Hospital for Children, 2 = = = , M.PeterMarinkovich,MD 2 = , Rajani Shelke, MS (JEB-GI) intermediate generalised 4, 39.8, DEB 22, EBS-MP 22, 8. There were 376 with DEB: RDEB DEB: with 376 were 8. There = 62, EBS-GI = = 10, 15 with Kindler syndrome and 27 with EB-NOS. 131. There were 675 with dystrophic EB (DEB): EB dystrophic with 675 were There 131. = = = 7, JEB-LOC 1 27.6, JEB , Lauren Richey, DVM,PhD 216, dominant (DDEB) =

= 15.6, DEB 22, EBS-MD 22, = = 34, EBS-LOC 2 0.11). , Zhiyi Cao, PhD = =

82, JEB-GI 9.5, EB-NOS = Our figures exceed figures Our Conclusions: =

10, JEB NOS 3 10, JEB 1.0, and all EB = 11, EBS-NOS 11, = 288, autosomal recessive = 2

= 13, JEB-PA NoorjahanPanjwani, = 419, DEB-NOS = 1.2. Comparing ear = 121, DDEB 121, = 2 3 , Michael Esmail, 25, with pyloric with 25,

Stanford Univer 4. There were 21 = 2

= 67. There 67. Tufts Uni-

14, JEB- = = = 27.7. 76.7, 76.7, = 238, 40. ------to scoringofocularscandatainpatientsforuseclinicaltrials. captures severityofdiseaseinmiceandcanbedirectlytranslated involvement waslowerthanexpected.Ournovelgradingsystem to specialhusbandryconsiderations. The asymmetryofocular survival rateisnearlydoublethetypicalrate,whichweattribute to weaning, and 75% reached the 20-week endpoint. Our overall Conclusions: Morethanhalfofthehypomorphicmicesurvived present. hemidesmisomes and fibrils, anchoring absent densa, the twoeyes(p mouse (17%) showed statistically significant asymmetry between Peñarrubia Sant JoandeDéuHospital(Barcelona) 1 INFLUENCE OF ETHNICITY? IS THERE EB: WITH ADOLESCENTS AN NUTRITIONAL PROFILEOF CHILDREN AND P108 Silvia Ricart with age, peaking at 41% of mice (24% of eyes) at 18 weeks. 18 Mean histologyscoresweresimilarbetweeneyes(2.14 at eyes) of (24% mice of 41% at peaking age, with prolapse. The prevalenceofcornealopacityinmiceincreased endpoint. The most common reason for early sacrifice was penile 20-week the to survived 75% photographed, mice 20 the Of 1). every 10-12 months doubled survival of the next round (see Figure were noted at 9,13,16,19,22, and 27 weeks. Refreshing the colony weaning age of 5 weeks. Declines in survival rate to less than 40% of 268 hypomorphic mice were produced, 146 (54%) survived to ages 4and14weekswascomparedwith WT mice.Results: hypomorphic mice oftwo Electronmicroscopy (t-test). eyes ween there wassomedegreeoflanguage orculturalbarrier. This fact All themalnourishedchildrenhad parentsofforeignoriginsand malnutrition. reached had 46.7% interventions), dietetic early EB careprotocolandnutritional approach(closefollow-upand and A). All the overweighted children have vitamin deficiencies (D, B12 >p90); all of them had JEB intermediate and were of Gypsy origin. patient was obese (BMI >p95) and 2 were overweighted (BMI One before. years 1,5 done was placement G-tube of indication medical the but age, of years 8 at placed G-tube a had patients anemia that need intravenous iron or blood transfusion. Both Morocco, 1 Pakistani). Two of them have refractory iron deficiency children (allRDEB)hadaweightbelowpercentile3forage(3 Eleven childrenhadnutritionalsupplementsprescribed.Four Caucasian. 26.7% and Gypsy 33.3% Pakistani, 6.7% Moroccan, 1 JEB generalized and 4 JEB intermediate. Family origin: 33.3% intermediate, generalized RDEB 2 severe, generalized RDEB 7 EB patients, aged between 3 months and 17 years, were included: origin ofthefamilieswerealsocollected.Results: ethnic and placement G-button of aage supplements, nutritional of use The recorded. were status vitamin and deficits selenium) zinc, (iron, oligoelements prealbumin), (albumin, parameters nutritional age), to related percentiles as (expressed index mass body height, Weight,(JEB). junctional and (RDEB) dystrophic in a reference pediatric hospital for severe EB patients: recessive Descriptive studyconductedinchildrenandadolescentsattended to compareitaccordingtheir ethnic origin. Materials& methods: nal statusofchildrenandadolescentswithsevereformsEB severe EB patients. The aim ofthe study is to describe the nutritio can influence the results of dietetic and nutritional interventions in morbidities. However, eating habits have deep cultural roots that delayed thedevelopmentofmalnutritionandotherderivedco Nutritional managementandearlygastrostomyplacementhave applied to health, natural history of infants with EB has changed. Introduction &objectives: With thedevelopmentoftechnology in therighteyeand2.83 Pediatric ComplexChronic Patient Unit, Conclusions: Evenallthepatientsunderwent thesame 1 , IsabelTorrús 1 , InésCases = 0.000). Electron microscopy showed no lamina 1 , Eduard Pellicer ± 1 , Asunción Vicente, Asunción 1.56 in the left eye, left the in 1.56 Acta DermVenereol Suppl220 1 2 , Silvia Ciprés Dermatology Service, 2 Posters p Fifteen severe = 0.243). One 0.243). 1 , Lucía

A total ± 1.49 69 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta search Institute,Boston,MA, 1 versity SchoolofMedicine,Boston,MA,USA, in eyes that received rhC7. Lower doses were also effective. Se after treatment.Results: and before photography lamp slit external and histology (EM), to quantify markers. Eyes were examined with electron microscopy Enzyme linked immunosorbent assay (ELISA) was then performed performed tocomparemRNA expressionofthesamemarkers. real-time singlecellpolymerasechainreaction(Rt-PCR)was Intensity ofstainingwascomparedusingimageJ.Quantitative (CTGF). factor growth tissue connective and (TGF-β1), 1 beta alpha smooth muscle antigen (α-SMA), transforming growth factor collagen VII, of presence for (IHC) immunohistochemistry with After 4 weeks, animals were sacrificed and corneas were examined control. Slit-lampexaminations(SLE)wereperformedweekly. doses). The contralateral eyereceivedBSSandservedasinternal 0.8 mg/ml rhC7 in BSS subconjunctivally every 48 hours (up to 5 from both eyes of 24 mice. The right eye was then injected with Therefore, the central corneal epithelium was necessarily removed epithelium. intact through penetrate not did rhC7 and tested first eyes ofmicewithDEB.Materials&methods:Topical dropswere describe theimpact of has not been tested in the eyes for efficacy or toxicity. Herein, we (rhC7) hasbeendevelopedtopotentiallytreatDEBinskinbut in patientswithdystrophic EB. Recombinant human collagen VII basement membrane results in abrasions, scarring and vision loss Introduction &objectives: Absent collagen VII within the corneal therapy. therapies that do not require removal of epithelium such as gene injury ischallenginginthisanimal model.Pathsforwardinclude Proof-of-concept thatrhC7leads to AF formationafterepithelial EM. on seen clearly not were cornea. (AF) the fibrils Anchoring opacity scoreswereconfoundedbyconjunctivalovergrowth of However, mice. hypomorphic in abrasion corneal after markers fibrotic reduces rhC7 of injection Subconjunctival Conclusions: conjunctivalization. showed eyes) (4/8 50% again but regimen, the to added was Steroid eyes). (5/10 50% in seen was surface rhC7 andcontroleyes.Conjunctivalovergrowth ofthecorneal between score opacification in difference no showed SLE and clear evidenceofbasementmembranenormalization.Histology “anchoring fibril candidates” were seen on EM, but there was no not inhypomorphicmice(repeatofELISA isinprogress).More reduction ofbiomarkerlevelsinresponsetorhC7 WT micebut were inconclusive. ELISA for α-SMA and TGF-β1 confirmed the results Rt-PCR treatment. after CTGF and TGF-β1, α-SMA, in miquantitative analysisofIHCsamplesdemonstratedareduction Vicki M. Chen, MD EPIDERMOLYSIS BULLOSA AFTER CORNEAL ABRASION INMICE WITH DECREASES MARKERSOF FIBROSIS RECOMBINANT HUMANCOLLAGEN VII P109 of culturalaspectsintheevolutiondisease. influence the recognize to important is it findings, these confirm would explain this finding. Although larger samples are needed to habits of this ethnicgroup in Spain and the less severe phenotype all wereGypsywithoutesophagealinvolvement. The dietetic caused a delay in the surgery. Of the overweight children (20%), and more concerns of the parents about G-tube placement, which could explain some difficulties in reaching therapeutic compliance 70 MD Cao, PhD Rajendra Kumar-Singh, PhD Tufts Medical Center, Floating Hospital for Children, 4 EB2020 1 2 , Abdulraouf Ramadan,PhD st WorldCongressonEpidermolysisBullosa 1 , Rajani Shelke, MS in vivo topical application of rhC7 to the All markerswereconsistentlyreduced 4 2 Stanford University, Palo Alto, CA , NoorjahanPanjwani,PhD 2 ,M.PeterMarinkovich, 2 , Ilene Gipson, PhD 3 Schepens EyeRe- 2 Tufts Uni- 2 , Zhiyi 3 - , Shiraz UniversityofMedicalSciences,Shiraz,Iran ramani patients, mostlyhavingapoorqualityoflife. can disturbthefunctionalandemotionalaspectsoflifeinthese EB study, this of results the to According of life.Conclusions: of patients had low quality of life and 21.2% had very low quality of thesedomains in men and women (p tional domain7.18 team attended their first adult appointment with them. amemberofthepaediatric andin3patients frombothservices visit to transferatthehospitaland3of themalsohadanjointoutreach choice of adult centre, 4 of them met an adult EB specialist prior transfer was17.6years. All 5youngadultswereinvolved inthe cohort hadseenamemberoftheadultteam. The meanageat choice of adult centre had been offered and 68% of the a paediatric cases of 44% In given. details contact and leaflets team adult an opportunity to discuss queries and concerns. Only in 50% were notes. 90% of young persons and 84% of their carers were given of casestherewasdocumentationthetransitionprocessin transition at 12 years of age. The started range was had 11 cohort – 16 paediatric years. the In 96% of (27) 64% service. adult the in people young male) 4 female, (1 5 and years 19 – 14 between aged service paediatric the in male) 20 female, (30 50 audited, Results: Paediatric toolhad22questions. We presentsomeoftheresults. the whilst questions, review 15 service. The had their tool Adult period andtherecordsofyoungperson’s currentlyintransition those whohadtransitionedintotheadultservicewithina2-year retrospective transitionaudittooltoreviewtherecordsofall rials &methods:Therespectiveteamsusedajointly-developed paediatric centresauditedtheircurrenttransitionpractices.Mate of the management of young people with EB. In 2019 our adult and ong conditionandtransitiontoadultservicesisanimportantpart Introduction &objectives:EpidermolysisBullosa(EB)isalifel Solihull Hospital EB Department,BirminghamChildren’s Hospital,EBDepartment, gerty, M.Ogboli D. James,K.Begum,Dewsbery,Light, C.Knowles, H. A. Hea- PROCESS INOUREBSERVICE TRANSITION OFOFTHE AGE:AUDIT COMING P111 The mean which 19weremenand14womenenrolledinthestudy. was usedforstatisticalanalysis.Results: of functionalandemotionaldomains.SPSSsoftwareversion18 consists which (EBQOL), questionnaire life of quality bullosa sampling method. The researchers used the specific epidermolysis EB agedover15years. The patientswereselectedbyconvenient cross-sectional study was conducted in 2016 among patients with quality oflifeEBpatientsinIran.Materials&methods:This the patients’ families. The aimofthisstudywastoevaluatethe genes intheskin.Itaffects severalaspectsofthepatient’s lifeand reditary skin disease caused bymutations in the collagen-forming Introduction ararehe (EB)is bullosa Epidermolysis &objectives: Mahdi Parvizi* Mohammad SECTIONAL STUDY EPIDERMOLYSIS BULLOSA INIRAN: A CROSS THE QUALITY OF LIFEINPATIENTS WITH P110 years. The mean years. The statistically significant difference between the mean the between difference significant statistically 1 domain was18.57 Medical Sciences, Shiraz, Iran, Molecular DermatologyResearch Center, ShirazUniversityof 2 , ZahraParvizi In total55youngpeople’s transitionpathwayswere ± standard deviation(SD)ageofpatientswas26 ± ± SD scoreofqualitylifeinthefunctional ± 8.15 (maximumscore 3.70 (maximum score (maximum 3.70 2 1 , Farhad Handjani 2 Health Policy Research Center, > Overall, 33 patients of patients 33 Overall, 0.05). Overall, 48.5% Overall, 0.05). = = 36) andintheemo 15). There was no was There 15). 1 , SoulmazGhah- Conclusions: ± SD scores ± 7.24 - - - -

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV RDEB patients. would be useful to develop new symptom relief therapies to treat novel players involved in the pathophysiology of RDEB, which TGF-β. to response the ted decreased the expression of pro-fibrotic markers and counterac fibroblasts RDEB in gene this of Overexpression attention. our tients. In particular, downregulation of PRELP in RDEB received contractile andsyntheticphenotypeincomparisontootherpa genes (e.g. PRELP, COMP, ALDH1A1, MMP3) and showed a less showed acompensationinthegeneexpressionofsomethese VII), type collagen of absence (despite phenotype mild very a with patient RDEB a from fibroblasts Remarkably, TGF-β. to greater expression of pro-fibrotic markers and increased response (ROS), species oxygen reactive of levels higher found and that membrane adhesion (PRELP), we analyzed the consequences of (COMP, MMP3, PLOD2), inflammation (IL1RL1) and basement related to redox imbalance (SOD3, ALDH1A1, HIF1A), fibrosis to TGF-β. Since RDEB fibroblasts differentially expressed genes sponse to mechanical stimulus, cellular contraction, and response associated with cytokine production, oxidoreductase activity, re were terms over-represented Furthermore, component. (ECM) concentrated in the extracellular space andtheextracellular matrix were fibroblasts RDEB and donor healthy between differences the disease.Results: a candidategenepotentially implicated intheprogressionof as PRELP overexpress to used was vector lentiviral a dition, ad In performed. was stress oxidative and TGF-β to response contraction, cellular markers, pro-fibrotic of expression as such by q-PCRand Western Blot.Phenotypicinvitro characterization pathways werecarriedout. Transcriptomic datawerevalidated ctional enrichmentanalysisofGeneOntologytermsandKEGG the same nullmutation and different clinical manifestations).Fun and 9isogenicpatientswithRDEB(includingtwosiblings analysis (RNA-Seq) of primary fibroblasts from 3 healthy donors pathways. Here weexploredindetailtheactualrelevanceofsomethese which allowed us to identify several altered signaling pathways. donors, healthy against fibroblasts RDEB of profile expression gene the compared have we modulators, disease-severity new component in the pathophysiology of this disease. In order to find Previous studiesrevealedacontributingroleplaybythedermal carcinomas. cell squamous aggressive and feet, and hands in deformitiesmitten healing, wound altered blisters, chronic with bullosa (RDEB)isaninheritedskinfragilitydisorderassociated Introduction &objectives:Recessivedystrophicepidermolysis 1 Esteban Chacón-Solano DYSTROPHIC EPIDERMOLYSIS BULLOSA PROGRESSION OF FIBROSISINRECESSIVE NOVEL PLAYERS IN THE ESTABLISHMENT AND P112 needs tobeaddressed. patient feedbackinformationinourprocessesatpresentandthis to increasetheuseofpatientinformation. We haveverylimited record keepingduringtheperiodoftransition.Ourteamsneed detailed more for need a identified it particular In improvement. showed areasofgoodpracticebuthighlightedforfurther rative provision for transition, this audit provided information that The Paediatricand Adult serviceshadawell-establishedcollabo Group, Fundación Jiménez Díaz (IIS-FJD) Madrid-Spain, Germany partment ofDermatology, Medical Center, Freiburg University, Marta García Madrid-Spain, ander Nyström Epithelial Biomedicine Division (UC3M-CIEMAT-CIBERER) Materials &methods: We performed ageneexpression 1,2 3 , FernandoLarcher , MartaCarretero 2 Regenerative Medicine and Tissue Engineering Enriched GO-termssuggestedthatmajor 1 , 2 , Francisco Quero This study identified study This Conclusions: 1,2 1,2 , MaríaJoséEscámez &Marcela delRío 1 , CarlosLeón 1,2 1,2

, Alex 3 De- 1,2 ------, drews, MD inberg School of Medicine, Chicago, IL, rie Children’s Hospital of Chicago, Northwestern University Fe- 1 MD behaviors toimproveoverallhealth outcomesinthispopulation. eating disordered of prevention and skills, coping image, body positive a encourage to peers/influences social and unit family in this population. Not to be underestimated is the role ofthe ideal. However, available screening tools have not been validated ED andrelatedconditionsinterveningwithearlytreatment is and relatedpsychologicalconditions.RoutinescreeningforDE/ for chronically ill EB patients should be aware of potential DE/ED nervosa, and dysfunctional eating. health. Additional cases described include food aversion, anorexia cause weightgain,despitechronicmalnutritionandoverallpoo r concern thatplacementofaGT wouldbevisibletopeersand use ofNGT orGT. Patientswearslimmingclothingandvoiced supplements, nutritional via “fat” becoming regarding concern patient and familial been has there adolescence, However,since and depression.StandardizedassessmentnegativeforanED. wounds chronic-non-healing dentition, GT,poor with blistering esophageal/oral deficiency, nutritional anemia, RDEB, with dentition anddepressionrefusalofGT; 28year-old woman poor strictures, esophageal supplementation, oral for drive low with intake oral poor and deficiency nutritional SCCs, multiple anemia, wounds, non-healing chronic RDEB, with woman old eating exemplify theseissues in thispopulation.Results: around delays functional and eating dysfunctional and DE/EDs, EDI-RF wereadministered.Otherexamples ofpatientsexhibiting Inventory; FunctionalDisabilityEDI-3SC;EDI-3; Body Dissatisfaction Assessment Scale;BeckDepression/Anxiety despite continuedseveremalnutritionanddeclininghealth. The signs of disordered eating and family dysfunction around eating, methods: body image in EB patients with chronic malnutrition. There arenopublishedreportsregardingDE/EDsanddistorted to bodyimage disturbance that can have detrimental consequences. disordered eating.CopingwithaCIduringadolescencecanlead for risk and eating over control of lack patient in resulting risks, children requiring nutritional interventions may also have inherent children/adolescents with CI 2. Involvement of caregivers with chronic illnessesshowedincreasedassociatedEDandDEin disorders (ED). A systematicreviewofliteratureondiet-treated increase patient risk for disordered eating (DE) and specific eating (CI) thatrequireatherapeuticdietornutritionalinterventioncan administration andpreventcomplications1.Chronicillnesses medication facilitate status, nutritional improve help may (GT) to severalcomplexandinterrelatedfactors.Gastrostomytubes molysis bullosa(EB)suffer fromnutritionalcomplicationsrelated Introduction & objectives: Patients with severe forms of epider N. Price,MD Harper EPIDERMOLYSIS BULLOSA A FIRST DESCRIPTIONINPATIENTS WITH AND BODY IMAGEINCHRONICILLNESS: EATING DISORDERS AND DISORDEREDEATING P113 2 Conviser JH, Fisher SD, McColley SA. Are children with chronic illnesses requiring 1 Zidorio APC, Dutra ES, Castro LCG, Carvalho KMB. Effectiveness of gastrostomy M. Fang, BS Center, Dell Medical School/University of Texas, Austin, TX, Mark P. Popenhagen, PsyD cinnati Children’s Hospital,Cincinnati,OH Phoenix Children’s Hospital, Phoenix, AZ, review. IntJEatDisord.2018;51(3):187-213. dietary therapyatriskfordisorderedeating oreatingdisorders? A systematic bullosa: asystematicreview. BrJDermatol.2018;179:42-49. for improvingnutritionalstatusandquality oflifeinpatientswithepidermolysis 2 We describe tworelatedyoungadultswithRDEB 1 , Daniela Russi, MD 2 , Moise L. Levy, MD 1 , JudithO’Have,PhD 1 , JennaRudo-Stern,PhD 1 3 , Kellie Badger, BS,RN , Anne Lucky, MD Conclusions: Providerscaring Acta DermVenereol Suppl220 3 Dell Children’s Medical 2 Ann & Robert H, Lu- 1 , LizLangreck, RD Posters 4 , Amy Paller,, Amy Materials & Materials & 1 , Israel An- , 29 year- 1 , Milie 4 Cin- 71 1 - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Worcester, MA of MedicineandHealthSciences TecSalud ITESM,N.L,Mexico mean age of 10.8 impact fromabrasions.Onsetofscarringandvisionlosswas with 73% of caregivers reporting moderate to extreme emotional high, was distress higher.Family or 8/10 of pain reporting 41% and pain), of level (narcotic 6/10 at severity pain reporting 88% months. Mean pain score with a typical abrasion was 7.8/10, with lasted 3 days or more, pain and for 43%, respondents, abrasions occurred every 1-4 of 70% For 5. age before abrasion first their tiano 1 bullosa (RDEB) is a severe inherited skin disorder caused by Introduction &objectives: Recessivedystrophicepidermolysis Joanna Jacków RIBONUCLEOPROTEIN COMPLEXES BULLOSA INIPSCELLSUSINGCRISPR/CAS9 OF RECESSIVEDYSTROPHIC EPIDERMOLYSIS EFFICIENT GENOME EDITING FOR CORRECTION P115 Mean age of onset for abrasions was 4.6 EB. junctional with 15% and EB dystrophic with 51% (60 caregivers of children and 35 adults), 37% with EB simplex, on-line. families through3majorEBresearchfoundationsandposted 62 questions, was internally validated, and distributed to 171 EB & methods:Thisinternationalcross-sectionalsurveyincluded complications. significant visually with factors these of relationship the examine to and abrasions, corneal EB-related this studyistocharacterizeandreportthepatientexperienceof of objective The life”. daily in function or feel patients how of evidence “provide to design study interventional in elements key a as marked specifically are instruments (ObsRO)” outcome tory”, “patient reported outcomes (PRO)” and “observer-reported his “natural the which in development, drug EB for guidelines United StatesFoodandDrug Administration (US-FDA)released ring and vision loss, has not been published. In June of 2019, the frequency, duration, severity, or cumulative number prior to scar onset, of age as such abrasion, of history regarding information pertinent Clinically 2004). (Fine JEB with those in years 5 by age 83.18% and 10, age by 63.53% reaches abrasions forcorneal risk cumulative the patients, RDEB In EB JEB. dystrophic and recessive (RDEB) in severe most is it but EB, of types Introduction &objectives:Ocularsurfacediseaseisseeninall Adam C. Tanaka, MPH OF AN INTERNATIONAL PATIENT SURVEY LOSS INEPIDERMOLYSIS BULLOSA:RESULTS VISION AND SCARRING CORNEAL ABRASIONS, P114 72 cet higher riskofvisionloss. affected, at significantly those are and lives daily whose patients recommended during comprehensive EB examinations to identify vision loss.Detailedinquiryregardingophthalmicsymptomsis Frequent abrasionsconferhigherriskofcornealscarringand from cornealabrasionsissevereandprolongedinmostpatients. ratio, (odds scarring corneal have Those withfrequentabrasionswere5.18timesmorelikelyto scarring occurred in 52% of respondents, and vision loss in 33%. 1 Satoru Shinkuma MD School of Medical and Dental Sciences, Niigata, Japan, USA, MA, USA, Department ofDermatology, ColumbiaUniversity, NewYork, Tufts Medical Center, Floating Hospital for Children, Boston, 1 , JungUShin 2 , Vicki M.Chen, MD 1 2 Division of Dermatology, Niigata University Graduate EB2020 1 Results: 2 University ofMassachusettsMemorialMedical Center, 1 , ZongyouGuo 1 2 , Corey Hansen ± st Ninety-five respondents completed the survey the completed respondents Ninety-five , JulioC.Salas-Alanis WorldCongressonEpidermolysisBullosa 11.3 and8.3 1 , MS, Calvin C. Robbins, BA 1 1 ± , HasanE. Abaci 1 , Ryota Hayashi 5.3 years, respectively. Corneal ± p = 4.9 years, 72% experienced 72% years, 4.9 0.001). 3 and Angela M.Chris- Conclusions: Pain 1 1 , Yudai Kabata , Yanne S.Dou- 1 , Karen Wiss, Materials 3 School 2 - - , therapeutic applicationsofgenecorrectionfortreatmentRDEB. hod represents a significant advance towards the development of for efficient gene editing via HDR (sgRNA) andsingle-strandedDNA asourrepairdonortemplate RNA guide synthetic modified chemically a with protein Cas9 ferentiation methods for iPSCs. We also utilized a GMP-certified and optimized. Here, we used xeno-free reprogramming and dif both efficiency and safety experimental aspects must be improved grafting. In order to translate this approach into the clinical setting, expression of C7 at the BMZ, and restored AFs at 2 months post- immunocompetent mice. These skinconstructsshowednormal to on grafted and (FB) fibroblasts and (KC) keratinocytes both generated from gene-corrected iPSCs that were differentiated into homozygous mutations.Results: derived from RDEB patients to target both heterozygous and Cas9-gRNA complex)ininducedpluripotentstemcells(iPSCs) Cas9-gRNAs systemusingRiboNucleoProtein-(RNP)(CRISPR- tered regulatoryinterspacedshortpalindromicrepeats(CRISPR) gastrostomy notoffered foreaseofuse.Results: cohort ofEBchildrenwithgastrostomies andonecentrewhere age. Thetool wasreviewed informally by one externalcentre It wasfeltthetoolnotreliable forchildrenunder2yearsof further informationshouldbeprovided andreferralconsidered. and its subtypes, enabled production of suggested scores at which professionals caringforthesechildrenandexperiencedwithEB ing preparedfortheprocedure.Reviewofthesescoresbyhealth children felt not needing gastrostomy and children currently be with gastrostomiesinsitu.Considerationwasgiventoscoresfor at clinicreviewsandretrospectivelyfortimeofinsertionthose antibiotic use for skin infections. This was piloted on 35 children: as wellpercentagebodysurfaceareaofwoundsandrecentIV use, dysphagia, hospital management of constipation and anaemia, geal strictures, reduced school attendance, nutritional supplement refusal or tears completing meals/medication, anaemia, oesopha growth, faltering including: occurrence assess to tool scoring a into developed were These insertion. after reported benefits and professionals providedalistofreasonsforgastrostomyplacement vice pathwayMaterials&methods:DiscussionsamongstHealth scoring tooldesignedtoassistthesediscussionsaspartofaser also beconsiderationsforgastrostomyplacement. We presenta may mealtimes stressful as such factors additional but EB, with assess severityofdisease andnutritional compromise forchildren to available Toolsprofessionals. are health and parents patients, cations andsurgery placementmake thedecisionchallengingfor term nutritional support. Limited outcome data, reported compli used for children with Epidermolysis Bullosa (EB) requiring long Introduction &objectives:Gastrostomytubefeedingisfrequently 1 R. Jones EPIDERMOLYSIS BULLOSA (EB) GASTROSTOMYWITH CHILDREN IN TUBE DISCUSSIONS FORINSERTION OF OFDEVELOPMENT A TOOLTO ASSIST P116 gene throughhomology-directedrepair(HDR). We usedtheclus exons 19 (c.2470insG) and exon 32 (c.3948insT) in the COL7A1 methods: no therapiesapprovedforthetreatmentofRDEB.Materials& negatively impactpatients’ qualityoflife. There arecurrently results inextensiveblisteringandopenwoundsontheskinwhich C7 andhaveseverelyimpaireddermal-epidermalstability. This membrane zone(BMZ).PatientswithRDEBlackfunctional basement the at (AFs) fibrils anchoring of constituent major the mutations in the COL7A1 gene encoding type VII collagen (C7), parment ofDermatology, BirminghamChildren’s Hospital Department ofDietetics, Birmingham Children’s Hospital, 1 , D.James Here, we demonstrated the correction of mutations in mutations of correction the demonstrated we Here, 2 , M.Ogboli 2

3D skinconstructs(SCs)were Conclusions: This novelmet For 35children 2 De------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV psychosocial life. Hence, quality of life is an important measure important an is life of quality Hence, life. psychosocial of aspects all on impact enormous an has EB research, previous of rarediseasescharacterizedby skinfragility. As indicatedin Introduction &objectives: Epidermolysisbullosa(EB)isa group Sigmund Freud University, Vienna, FacultyofPsychology Gudrun Salamon, Alexander RuberlandLauraMaar SYSTEMATIC REVIEW BULLOSA AND QUALITY OF LIFE. A PSYCHOSOCIAL ASPECTS OF EPIDERMOLYSIS P119 well asthedevelopmentofnoveltherapeuticapproaches tool to study early RDEB-cSCC development and progression, as valuable a offers model tumor RDEB-cSCC-iPCC the together, a tumorsformedbyRDEB-cSCC-iPCCs.Conclusions:Taken to testruxolitinibforitsinvivoactivityreversethegrowthof model a as used and characterized be will they develop, tumors constructs (SCs)andgraftedontoimmunocompetentmice. After cancer stemcells(CSC)andwillbeusedtogenerated3Dskin RDEB-cSCC-iPCC undergo differentiation intoRDEB-cSCC- the RDEB-cSCC-iPCCscorrelatedwithstemcellstate. The that demonstrating fibroblasts human normal from generated signatures ofRDEB-cSCC-iPCCsweresimilarto WT-iPCCs Moreover, TaqMan assays of human stem cell pluripotency gene and TRA-1-60, and the ability of the cells to differentiate expression of pluripotency markers such as Sox2, Oct-4, SSEA-3 the efficiency, colony-forming morphology, epithelial-like by cSCC afterinfectionwithasingleLV vectorwasdemonstrated cSCCs. in cSCCs derived from RDEB patients to generate iPCCs from lentiviral (LV) vectortoreducethenumberofviralintegrations this study, we used a humanized version of the single polycistronic low. very is efficiency reprogramming cer. Due to the genetic and epigenetic barriers in cancer cells, the undergo changesreminiscent withthestagesofearly-onsetcan wound they cSCCs, into back differentiate to allowed then and hypothesized thatifcSCCcellswereconvertedtopluripotency the epigenetictransformationprocessduringtumorigenesis. We novel toolusedtoinvestigatecancerprogressionandunderstand cancer cells into induced pluripotent cancer cells (iPCCs) is a mortality ratesinthesepatients.Reprogrammingdifferentiated recessive dystrophicepidermolysisbullosa(RDEB)leadstohigh squamous cellcarcinoma(cSCC)anditsrapidprogressionin Introduction &objectives: The earlyonsetofaggressivecutaneous Department ofDermatology, ColumbiaUniversity, NewYork, NY Angela M.Christiano Joanna Jacków, Ryota Hayashi, Avina Rami, Zongyou Guoand INITIATIONPROGRESSION AND CANCER CELLSFORSTUDYING RDEB-CSCC DERIVEDINDUCEDPLURIPOTENT P117 regional factorssuchaswaiting-listtimes. as predictor of optimal time for gastrostomy referral, considering procedure ifsupported.Furthervalidationisplannedtoassessuse potentially guideoptimaltimeofinsertionatEBcentreswherethis annual assessmentwiththistoolcancontributetodiscussionsand to make. Few resources are available to assist with this. We believe be a difficult one for health professionals to guide on and families surgeon ≥ severe. A Score of ≥ generalised severeand27EBrecessivedystrophic- 0 -70 median 35. EB subtypes included: 2 junctional EB, 3 EBS- range calculated was score a 7) median years range1.5-7.0 (age 40 were suggested to prompt further education and referral to referral and education further prompt to suggested were 40 Conclusions: The decisionforgastrostomyplacementcan Results: Successful generation ofiPCCs from RDEB- 15 for growth section only and/or total score Materials &methods:In in vitro. - of EBandtheircorrespondingcopingstrategies. Our systematic review identifies and explores psychosocial aspects highly individualandvarywidelywithinpeoplelivingwithEB. decision-making. flexible and assessment impact situational needs It pain. of spite is linkedtodecisionsinfavourofphysicalorsocialactivities to liveaclose-to-normallifeoratleastmoments to enhanceknowledgeandunderstandingofothers; The attitude communicating the personal health situation are helpful in order for Strategies EB. with people with and condition, comparable care professionals, with healthy people, with people in a similar/ and easierwhentakinganactiveroleintheexchangewithhealth highly appreciated;Interactionwithothersisagreatresource is care, wound for routines helpful e.g., in, experience personal and knowledge specific on based case EB member’s family a or own the for expertise the of validation self-efficacy. The and emotion regulationandispositivelycorrelatedwithself-esteem the impactofEBreliesonstrategiesfordealingwithpainand external support(likecareassistance)whennecessary;Containing can beincreasedbyactiveEBmanagementandthehelpof autonomy,with associated is which life of Control level: coping psychological aspectsweredescribedashelpfulonanindividual the focus on EB patients ortheir families. with studies case single and methods mixed qualitative, tative, and clinical metrics including visual acuity, abrasion frequency,acuity,abrasion visual including metrics clinical and findings OCT between associations as well as lesions, corneal the abilityofcorneal AS-OCT imagingtovisualize EB-associated USA). WeCA, Fremont, Inc., examined (Optovue, OCTsystem ophthalmic photographeronthe OptovueRTVue-XR Avanti SD- tested monocularly. AS-OCT imageswereacquiredbyatrained questionnaire wasgiventoallsubjects. Visual acuity (VA) was symptoms” abrasion and “vision 2018. A10-item USAin zona, during the3-daylongDEBRA careconferenceinPhoenix Ari corneal pathology. Materials & methods: Patientswererecruited cornea. We developedanon-invasivetooltoassessEB-associated the of imaging three-dimensional and cross-sectional resolved, coherence tomography (AS-OCT) provides high-resolution, depth- optical segment Anterior therapy. to response in modification disease of assessment objective limits which biopsied, easily not is cornea the skin, Unlike use. ophthalmic for readiness and application skin between distance great a remains there skin, in Introduction &objectives: As therapiesforDEBmakeprogress Tufts MedicalCentre Research to Prevent Blindness,FloatingHospitalforChildren at coma foundation, Massachusetts LionsEye Research FundInc, Sigillum Universitatis Tuftensis Pax Etlux 1852, Children’s Glau- K. Waheed, MD,MPH,Vicki M.Chen,MD Nihaal Mehta,BA,CalvinRobbins,Elizabeth Noh, BS,Nadia EPIDERMOLYSIS BULLOSA OPTICAL COHERENCE TOMOGRAPHY IN ANTERIOR SEGMENT SPECTRAL DOMAIN P120 selection of 38 papers presenting original work, comprising quanti of literature. A set of exclusion and inclusion criteria led to a final review systematic a conducted thoroughly,we strategies coping order to address all psychosocial aspects of EB and corresponding lead tosocialandemotionalchallenges.Materials&methods:In restrictions Additionally,life. these everyday in restrictions and caused is by chronic stress pain, EB, the need In of intensive situations. wound challenging management to and stress to options strategies areanindividual’s mentalorbehaviouralresponse balance between personalresourcesand challenges faced. Coping applies to the concept of same wellbeing, which The describes perception. the individual individual by influenced highly is life of in psychological as well as in clinical research. However, quality Conclusions: Qualityoflifeandwellbeingare Acta DermVenereol Suppl220 Results: Posters The following 73 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Furthermore, the treatment resulted in rapid pain relief (Eplasty. and rapidhealingwasachieved without recurrence for 2 years. spond toatwiceweekmatrix therapy treatmentuntilcomplete re to reported was EB, Bullosa, Epidermolysis recessive with male old year 12 A (doi:10.1001/jamaophthalmol.2016.3019). corneal ulcerswithsimilarhealingandpainreliefobservation treat to developed also was product based OTR4120 similar A relief associatedwiththisimprovedhealingwasalsoobserved. 9744-5). Interestingly, no adverse effects were reported and pain 10.1007/s10719-016- (doi: publications several in reported and of patientstreatedforchronicskinulcersvariousorigins was furtherobservedoverthelast5yearsintensofthousands vement in speed, quality and resistance to breakage. This efficacy surgical, ischemic and burn skin wounds, showing healing impro is supportedinseveralanimaltissuelesionmodelsincluding meostasis and repair. Efficacy of OTR4120-based Matrix Therapy the ECMmicroenvironmentconditionsnecessaryfortissueho newly produced growth factors and cytokines, thereby restoring thedamaged ECM, and provides storage and protection to the local of proteins matrix the bridges HS, destroyed the replaces gistered as OTR4120. Introduced at the site of injury, OTR4120 re polyglucosecarboxymethylsulfate 1-6 alpha HS, mimicking repair. We haveengineeredbiodegradablenano-polysaccharide differentiation thatareallrequired fortissueregenerationand pivotal role in the regulation of cell proliferation, migration and protector sites to most of the communication peptides, playing a matrix proteins such as collagens, laminin etc.. and as storage and of the ECM scaffold which act both as linkers, bridging structural of cellularregeneration.Heparansulfates(HS)arekeyelements croenvironment maintainstissuehomeostasisbylocalregulation Introduction & objectives: The Extra Cellular Matrix (ECM) mi University ParisEstCreteil, OTR3 Barritault Denis PROCEDURE FOREPIDERMOLYSIS BULLOSA THERAPY IN A NEW WOUND MANAGEMENT RATIONAL FOROTR4120-BASEDMATRIX P121 nostic guidance. to interventions. Larger longitudinal studies are neededforprog offer objectiveassessmentofcorneal surfacediseaseinresponse used inthedesignofclinicaltrialsophthalmictherapeuticsto can span the entirety of the corneal stroma. These findings may be of depth, length and number of discrete lesions per eye. Scarring quantification quadrant, superior the of sparing fibrosis, stromal findings include epithelial hypertrophy (not atrophy) over areas of significantly different than those of age-matched controls. Novel clusions: This studydemonstratesthateyesofpatientswithEBare associated with increased stromal, not epithelial, thickness. was Visionloss patients. any in seen not was atrophy quadrant, inferior the in significant was hypertrophy Epithelial quadrant. superior the spared fibrosis Stromal cornea. the of zones 9-mm and 7- 5-, central the in fibrosis) (stromal thickening significant controls (p cantly more prevalent and numerous in EB patients compared with vs. 15.00 years, (1.80 controls than patients in lower significantly was abrasions 0%, vs. (9.7% controls (p pain ocular of severity and abrasions, of duration abrasions, of frequency abrasion, last since time for: seen were controls and statistically and clinically significant differences between patients Highly 11.3%. JEB 8.1%, DDEB 59.7%, RDEB 21%, Simplex were included for final analysis. Distribution of EB subtypes was duration and pain. 74 = 0.0000). Amblyopia was substantially higher in patients than EB2020 1 = 0.0000). Six of the nine sectors showed statistically showed sectors nine the of Six 0.0000). p st = Results: WorldCongressonEpidermolysisBullosa 0.0004). Discrete fibrotic lesions were signifi p = In total, 62 EB patients and 60 controls 0.0132). The median age for onset of onset for age median The 0.0132). Con ------antimicrobial properties (including fungal, and ESKAPE patho ESKAPE and fungal, (including properties antimicrobial expression. Ceragenins mimic the behavior of LL-37, displaying paired wound-healing, which improves with activation of LL-37 im to leading LL-37, of expression reduced shown have EB of against infectionandtofacilitatewound-healing.Invitromodels trophils and epithelial cells, endogenously generated as protection neu in expressed primarily peptide, antimicrobial characterized Introduction &objectives:HumancathelicidinLL-37isawell- versity, Provo, UT, CalvaryPharma,Chandler, AZ Department ofChemistryandBiochemistry, BrighamYoung Uni- Michael Moore andPaulSavage THERAPEUTICS FOREB ANTIMICROBIAL PEPTIDES, AS NOVEL CERAGENINS, MIMICSOF ENDOGENOUS P122 to beavaluabletherapeuticfor EB lesions. lend support to the hypothesis that Ceragenins have the potential pathology, EB in LL-37 of role the given results, experimental spray, avoiding friction that exacerbates blister formation. These standard topicalcreams) are formulated for delivery as an aqueous (unlike Ceragenins Additionally, treatment. standard-of-care to especially evident in refractory wounds that are otherwise resistant wound-healing, promote to ability significant indicate 2 study and anti-inflammatory properties of ceragenins. Data acquired in counts anderythemafromstudy1areconsistentwithbactericidal compared tothecontrolgroup.Conclusions:Reducedbacterial wounds reachedfullclosureattheendof8-weektimepoint twice as quickly. Furthermore, a larger portion of the CSA-treated wound area compared to vehicle-treated wounds, healing almost with CSA-44trendedtowardfasterhealingintermsofreduced counts andcontinuedtodisplayerythema.Study2. Wounds treated treated burns.Silversulfadiazine-treatedburnshadlarger bacterial CSA-44 in seen was erythema minimal and burden, bacterial in were measuredweekly. Results: twice dailywithCSA-44forrelatedfootulcers. Wound areas 7 days. Study 2. Patients with type II diabetes received treatment for administered were sulfadiazine, silver and CSA-44, of tions with Pseudomonasaeruginosa. Treatment with variousformula inoculated administeredinaporcinemodelandsubsequently were extremity ulcersMaterials&methods:Study1.2nddegreeburns as anadjuncttostandardcareintreatingchronicdiabeticlower CSA-44 ceragenin of efficacy and safety the evaluate to study 2. Study models. Avehicle-controlled double-blind randomized, burn porcine in ceragenin, lead a CSA-44, of capacity microbial are describedbelow. Study 1.Pre-clinicalassessmentoftheanti therapeutic. Multiple studies support this hypothesis, two of which control, Ceragenins have potential for development as this optimal demonstrable mimicryofLL-37inwound-healingandinfection and acceleratingwoundhealingthroughcellmigration.Giventheir and pain resulting from chronic blisters, while preventing infection clinical need for EB is a therapeutic with ability to alleviate pruritis gens), anti-inflammatory and wound-healing properties. The unmet for EBpatients. adapt this technology to a specificwound management procedure on themarket. We nowpresenttherationaleandfutureplansto Therapy technologyinEBuntilasprayformbecameavailable Matrix OTR4120-based the of evaluation the delay further to of an impregnated gauze was not adapted and it was decided consisting device based OTR4120 original the of use the cases, Despite these encouraging responses also observed in other EB (doi:10.1111/iwj.12074)wounds.syndroms Bluefarb Steward of ulcers in patients with sickle cells (doi:10.1111/iwj.12217) and closure were reported following years ofunsuccessful treatments stableand relief pain closure, successful Similar 2012;12:ic15). Study 1. The largest reduction - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Palo Alto, CA Palo Alto, 1 Khuu ton, PA, bullosa (RDEB)patientshave mutations intheCOL7A1gene Introduction &objectives: Recessivedystrophicepidermolysis E. Gorell BULLOSA FOR RECESSIVEDYSTROPHICEPIDERMOLYSIS CELLTHERAPYCORRECTED AUTOLOGOUS PHASE 1/2A CLINICAL TRIAL OF GENE- P124 to initiationofaPhase3trial. favorable safety profile and wound healing efficacy, thus leading demonstrate that genetically engineered fibroblast therapy has a data anesthesia orinpatienthospitalization.Conclusions:These general require not did injections fibroblast engineered tically Gene weeks. 25 or 12 4, wounds at closure control wound complete the achieved of none contrast, In weeks. 52 and 25 of (≥ two additional wounds showed almost complete wound closure and closure wound complete showed (5/10) 50% weeks, 12 At ≥ by defined as weeks, 80% (8/10) of wounds showed significant wound healing and no significant antibody responses to C7 detected. At 4 and 12 serious adverseeventsorreplicationcompetentvirusdetected and wereseeninasubsetoftreatedsites.Notreatmentemergent pression atthedermal-epidermaljunctionandrestorationof AF cm prior todosing. These chronicwounds ranging insizefrom4.3 were showntobeopenateachmonitoringvisitup8months obtain a sufficient quantity for study treatment. Wounds in study vector encodingthewildtypeCOL7A1geneandexpandedto were transduced with a third-generation self-inactivating lentiviral (EM). Autologous RDEB fibroblasts isolated from skin biopsies and a lack of intact anchoring fibrils (AF) by electron microscopy tectable C7 expression by immunofluorescence microscopy (IF) trial carried various null COL7A1 mutations resulting in unde methods: an We reporttheresultsofongoingPhase1/2clinicaltrial mutations in the COL7A1 gene encoding type VII collagen (C7). Bullosa (RDEB)isaninheritedgeneticskindisordercausedby Introduction &objectives:RecessiveDystrophicEpidermolysis M.P. Marinkovich BULLOSA (RDEB) RECESSIVE DYSTROPHICEPIDERMOLYSIS INJECTED INTO THE SKINOF PATIENTS WITH AUTOLOGOUS HUMANDERMAL FIBROBLASTS CORRECTED, COLLAGEN VII EXPRESSING A PHASE1/2STUDY OF GENETICALLY- P123 veland, OH, 1 Hospital forChildren, Portland,OR, lyala *[email protected] Nguyen kawa 25, 12 and 4 weeks after initial treatment session. treatment initial after weeks 4 and 12 25, 52, at wound target the in session treatment second a received a singleintradermaltreatmentsessionatbaseline.Foursubjects injected with gene-corrected fibroblasts. All six subjects received tolerated through52weekspost-administration.LinearC7ex primary endpointwastoevaluatesafetyandtreatmentwell Stanford University School of Medicine, Stanford, CA, Stanford University, Stanford, CA, 95% wound closure). This trend continued to later time points ex vivogenetherapyforthetreatmentofRDEB.Materials& 2 to34.1cm 3 1 1 , M.Spellman , M.P. Marinkovich , D.Keene 2 4 , Z.Siprashvili Veterans Affairs Medical Centre, Palo Alto, Stanford, CA, 1 , S.Eichstadt Five adultandonepediatricsubjectsenrolledinthis 3 Shriner’s, Portland,OR, 2 75% wound closure as compared with baseline. with compared as closure wound 75% aswellintactskinsiteswereintradermally 3 , K.Rieger 1,4 3 *, A. Lane *, A. , J.Maslowski 1 1 , M.Barriga , J. Nazaroff 1 , 4 , J.Y. Tang 1 , R.Khosla 1,3 , K.Sridhar 3 1 1 2 , A. Ponakala , A. 1 Abeona Therapeutics,Cle- 3 , A. Chiou , A. Castle Creek Pharma,Ex- 4 VeteransHospital, Affairs 1 , H.P. Lorenz 1 , D.Keene 1 , L .Taylor 1 , C.Teng Results: 1 , L.Furu- 2 2 , A. Ma- , A. Shriners 1 1 The , N. , P. - - - cm (35 These gene-correctedautologousepidermalsheetsmeasured5x7 with aretroviruscarryingthefull-lengthhumanCOL7A1gene. biopsies. Epidermalsheetswerepreparedfromcellstransduced fromparticipantskin wereisolated keratinocytes Autologous 7 adultparticipants(n Zurich, Switzerland Paediatric Dermatoloty, UniversityChildren’s HospitalZurich, ger-Briel patient-reported outcomes. and promotedwoundhealingthatwasassociatedwithimproved gene–corrected autologouscelltherapy. This approachwassafe years. 3 at (0/16) 0% and years, 2 at (2/27) 7% 1, year at sites treated of (5/26) 19% to compared wounds of (23/38) 61% in present was itch treatment, to Prior years. 3 at (0/16) 0% and years, 2 at (1/27) 4% year, 1 at sites of (0/26) 0% in pain reported cipants ≥ healing wound with sites treated At sites. wound of (20/38) 53% in pain reported participants treatment, to Prior restoration wasseenonskinbiopsyat2yearsinparticipants. with 17% (1 of 6) of control wounds (p compared healing greater or 50% had wounds treated of 38) of (p wounds control of 6) of (1 17% 38) of treated wounds had 50% or greater healing compared with control woundsat6months(p 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated 50% or greater by Investigator Global Assessment was present in experienced anyseriousrelatedadverseevents. Wound healingof cipants werefollowedforupto5years.Results:Noparticipants for 6days. Wound sizedecreased from9.48cm wound was treated twice daily with Oleogel-S10 and foam dressing type 2 diabetes with a chronic scrotal wound for 3 months. The (>21 day).Results: were treated using Oleogel-S10 1mm thickness for chronic wounds remodelling. The followingfourcaseswithdifferent typesofEB and proliferation inflammation, healing: wound of stages classic the of three of activity has Oleogel-S10 sensitization. for allergic potential low a have components Both oil. sunflower with preparation from birch bark containing 10% triterpene combined a is tion ofthefragileskin.Materials&methods:Oleogel-S10, is primarilysymptomaticwithoptimalwoundcareandprotec effective pharmacologicalorgenetictherapyexists. Treatment No wounds. nonhealing and membranes mucous blisters, skin by fragility ofepithelial tissuesandrepeateddevelopmentof a heterogeneousgroupofchronicskindisorderscharacterized Introduction & objectives: Epidermolysis bullosa (EB) describes Stella Gewert CASE SERIES EPIDERMOLYSIS BULLOSA (EB)– A 4-PATIENT FOR THETREATMENTOLEOGEL-S10 OF P125 ningful benefit of treating chronic RDEB wounds with This studyprovidesadditionaldatatosupporttheclinicallymea improvement in patient-reported pain, itch, and wound durability. atment. Treated wounds with 50% or greater healing demonstrated 1 gene-corrected autologous cell therapy. and patient-reportedoutcomesinRDEBpatientstreatedwith safety,efficacy, long-term the evaluated study open-label 1/2a have markedskinfragilityandblistering. This single-centerphase and thus lack functional type VII collagen (C7) protein; they wound, and extensive pruritus. Treatment consisted of antihista pruritus. Treatmentof extensive consisted and wound, crusted blisters, herpetiform annular, abdomen lower and back improved rapidly. 2.4year-old male withEBsimplexupper re-epithelialized withinthetreatment period.Painanddiscomfort tre, UniversityofFreiburg, Freiburg, Germany, Department of Dermatology, Faculty of Medicine, Medical Cen- C7 expression persisted upto2yearsaftertre persisted C7expression Conclusions: 2 , FranziskaSchauer 2 ) andweretransplantedonto6woundsitesineachof 1 , Dimitra Kiritsi 1. 57year-old malewithdystrophicEBand = 42 sites total) from 2013 to 2017. Parti 2017. to 2013 from total) sites 42 1 1 , Hauke Schumann < 0.0001). At year 1, 68% (26 of (26 68% 1, year 0.0001). At Acta DermVenereol Suppl220

= 0.025). At year 2, 71% (27 71% 2, 0.025). year At = 0.019). Evidence of C7 Materials & methods: 2 to 0.65 cm 1 Posters , Agnes Schwie , Agnes 2 Deaprtment of 50%, parti 50%, ex vivo 2 and , C7 75 ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta clinicaltrials.gov NCT03068780). EB-related woundsinpatientswithdifferent typesofEB(www. in Oleogel-S10 of effectiveness and safety the assess will study improved inthesepatientsduringtreatment. The phaseIIIEASE patients. Dressingrequirementswerereducedandqualityoflife in thetreatmentofEBwoundsfourselectedindividual site. Oleogel-S10 healed faster; itching and pain persisted at the control S10. After 5 weeks, both wounds healed. The wound treated with control woundbelowtherightkneewastreatedwithoutOleogel- S10, fatty gauze and foam dressing at home – an intra-individual EB. A lateralleftanklewoundwastreateddailywithOleogel- on extremities andbodyassociatedwithrecessivedystrophic girl with permanent, spontaneous and trauma-induced blistering, (Oleogel-S10 stopped), wound healing deteriorated. 4. 12 year-old treated withdressingalonedidnotreduceinsize.Postdischarge be awareofskinchangesoverbony prominences. of pressure damage and is anticipated patients check their skin and patients and carers, it will start the conversation to raise awareness Conclusions: This patient leaflet is hoped to be a good resource for awareness ofpressureulcerswithinthisveryuniquepopulation. will thenbegiventopatientsandcarersishopedraise becoming readily available within the EB community. The leaflet Following this the leaflet is presently awaiting final sign off before was thengiventosomepatientswithEBforcomment/feedback. tations were made as required following the feedback. The leaflet was created and shared within the EB multidisciplinary team, adap responsibility fortheirowncare.Results: to discuss concerns, thus empowering the patients/ carers to take the conversationaboutpressureulcersandallowanopportunity start will leaflet the of introduction the hoped is it concerned, if contact to who regarding information contains also leaflet The damage occursearlyinterventionandtreatmentcanbeprovided. hoped thatpressuredamagewillbepreventedorifany compared to a pressure related wound. With this information it is mon locationsandthedifferences betweenanEBrelatedwound com damage, pressure identify help damage, pressure of causes is, ulcer pressure a what explain to family and carers patients/ to information give to is leaflet patient the of purpose lenging. The skin lossthisthenmakeidentifyingpressuredamageverychal superficial and blistering as presented often are wounds damage pressure In loss. skin superficial and blistering as present often pressure damage is key. In EB the patients experience wounds that carers andfamilyareinformedknownthewaystoprevent Pressure ulcers are in large preventable harm and ensuring patients, treatment isinplaceatimelymanner. Materials&methods: ensure patients and carers are informed and correct management/ to EB with patients for prevention ulcer pressure for leaflet tion losa (EB). This encouraged the development of a patient informa challenging especiallywithpatientswhohaveepidermolysisbul Introduction &objectives:Identifyingpressuredamagecanbe Guy’s &StThomas’ NHSFoundationTrust Samantha Wharton EPIDERMOLYSIS BULLOSA (EB) PRESSURE ULCERPREVENTION AWARENESS IN P126 cm 13.63 from reduced size wound edges, wound between bridges epithelium developed wound the hours, Treatment consisted of Oleogel-S10 and foam dressing. After 48 neck andarms. Various secondarycomplicationswereevident. 3 year-old girl with chronic, junctional EB wounds on body, face, polidocanol or urea ointments), pruritus increased immediately. 3. over 3 months. Once Oleogel-S10 was discontinued (switched to mine and Oleogel-S10. Blistering, erythema and pruritus improved 76 Oleogel-S10 was effective and well tolerated well and effective was Oleogel-S10 Conclusions: EB2020 1 st WorldCongressonEpidermolysisBullosa A pressure ulcer leaflet 2 to9.58cm 2 . Wounds - - - - - Monterrey mas JeffersonUniversity A McGrath 10 cases in 2014, today I have 120 of all genders, ages 0-35, in 0-35, ages genders, all of 120 have I today 2014, in cases 10 cases. EBisnotcoveredbyanymedicalinsurance.Startingwith EB with deal to able are different who in fields doctors qualified for hand and teeth surgeries, blood transfusions and to recommend patients in Egypt, to spread awareness, provide medications, pay EB for name her under foundation charity a established away,I paintings togovernmentalhospitalsforresearch. When shepassed as theyoungestEgyptianartist.Shedonatedrevenuesfromher through three exhibitions during her short lifetime and was known drawing exhibition at the age of 9. She spread awareness about EB of 5, we discovered her talent in drawing, and encouraged her first Yasmin tried to lead a normal life, despite her disease. At the age ElSadat mother of Yasmin ElSamra, born with RDEB (1997-2012). and in some cases lethal before the age of 30. My name is Hanaa debilitating pervasive, often painful, always is EB cure. no with all threemajorformsof dystrophic EB.Itisarareskin disease minor injuriesorfrictions.MutationsintheCOL7A1genecause blistering easily. Blistersandskinerosionsforminresponseto losa (EB) is a genetic condition that causes the skin to be fragile, are who Egypt referred to me bydermatologists. Results: in (120) patients EB help to RDEB with born 2014 under the name of my daughter Yasmin Elsamra (1997-2012) Introduction &objectives:Establishinga charity foundation since Yasmin ElSamraEBFoundation Hanaa Elsadat EB INEGYPT YASMIN ELSAMRA CHARITY FOUNDATION FOR P127 bullosa (RDEB) is a debilitating skin blistering disorder characteri Introduction &objectives: Recessivedystrophicepidermolysis CRUK BeatsonInstitute Jasbani H.S. Dayal EPIDERMOLYSIS BULLOSA ARISING INRECESSIVEDYSTROPHIC CUTANEOUS SQUAMOUSCELL CARCINOMAS SIGNALLING INLIFE THREATENING HETEROGENEOUS ADDICTION TO TGFΒ P128 about EBwithprideandselfconfidencetopeoplemedia. better withcareandlove. They alsofeelproudmakingawareness and psychological way,I see their wounds and blisters are healing lasting legacy. Conclusions: Advising themwithgoodnutrition cure. a Yasmin’sa leave always will foundation her and mission smiles on their faces, giving them hope that one day there will be for thebetter. FeelinghappywhenIrelievetheirpainandseethe changes lifestyle their while pride, with illness their about ness I see their wounds and blisters decreasing, as they spread aware money and feel that they have the right to live happily. own their Conclusion, earn to businesses, small handle to them encouraging and competitions drawing bazaars, charity in participating and psychologically, through drawing, crafting, story writing, dancing Society. Iaddressedthisinthrough goodnutritionaladviceand because oftheirappearanceanddisabilitywhentheyintegratein pain we feel. It is their mind and the way people perceive them EB Yasmin, I had the feeling that their pain was different from the them allmedicalneeds.Basedonmyexperienceasamotherof offeras, well as children, their handle to how mothers teach and referred tomethroughdermatologiststhattrustIcanadvise cluding some cases from different Arab Countries. EB patients are reth J.Inman 3 ,King’s College London 4 , Richard Tylor 1,2,5 1,2 , SusanMason 6 1

,University ofDundee 2 , Karen Blyth 4 , University of Glasgow 1 , Julio C. Salas-Alanis 1,5 , Andrew P South Epidermolysis Bul 2 ,Universidad de 3 5 , John , Tho- 6 , Ga- - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV respond to pre-treatment with SB-431542 mice. Cells promoted by SB-431542 in in-vitro assays did not France , netics, Necker-Enfants Malades Hospital, Paris,France patients, and notably by distinguishing the clinical outcome of the characterize thegenomicalterations incSCCoccurringRDEB (cSCC) leadingtoprematuremortality. The aimofourstudyisto development ofaggressivecutaneous squamouscellcarcinoma cations. The mostseverecomplicationinRDEBpatientsisthe formation and erosions resulting in local and systemic compli with RDEBdisplayskinandmucosa fragilityleadingtoblister mutations inCOL7A1encodingtype VII collagen.Patients bullosa (RDEB) is a severe hereditary skin disease caused by Introduction &objectives:Recessivedystrophicepidermolysis Hélène Ragot PATIENTS SQUAMOUS CELL CARCINOMA OF RDEB GENOMIC ALTERATIONS INCUTANEOUS P129 cSCC patients RDEB of subset a in signalling TGFβ of benefits suppressing inhibitors should proceed with caution due to the potential tumour ment with TGFBR1 kinase inhibitors.Clinicaluseof TGFBR1 patients astheyexhibitheterogeneityintheirresponsetotreat cSCC RDEB of subset a only for benefits therapeutic potential in RDEBcSCC.Conclusions:Inhibiting TGFBR1 signallinghas biomarkers and shed light on the potential role of TGFβ signalling validation of candidate genes will help identify key downstream gene expressionfollowingtreatmentwithSB-431542.Ongoing cell lines (RDEB62/70 cSCCK) showed significant differences in cing analysisofapromoted(RDEB2cSCCK)andtwoinhibited 5 weeks post injection ( lower significantly also was volume Tumour control. vehicle to Kaplan Meir)followingpre-treatmentwithSB-431542compared inhibited in in-vitro assays, was significantly enhanced (p cells, with injected subcutaneously mice SCID of survival all over where findings in-vitro our confirmed experiments In-vivo (n abletopromote(n also activitywas kinase of endogenous TGFβ signalling. However, inhibition of TGFBR1 (n cSCCKs RDEB of 63% of invasion and migration potential, clonogenic Proliferation, inhibitor responses in RDEB cSCCprimary keratinocytes. Results: understand the mechanism underlying the specific TGFBR1 kinase RNA sequencingwasperformedusingtheIlluminaplatformto xenografts. subcutaneous in-vivo using confirmed were findings vitro In AstraZeneca). (AZ12601011, AZAO1 and SB-431542 with TGFβ1 and its type 1 receptor (TGFBR1) kinase inhibitors, tissue andusedinarangeofinvitroassaysfollowingtreatments Primary keratinocyteswereisolatedfromRDEBcSCCpatient peutic interventioninRDEBcSCCpatientsMaterials&methods: inhibiting thera of for application signalling potential TGFβ the signalling fortherapeuticinterventioninRDEBcSCC.Investigate of TGFβ use the investigate we Here patients. these in promoter it is not known whether TGFβ functions as a tumour suppressor or Growth Factor β (TGFβ) signalling is Transforming elevated 55). in of RDEB age cSCC but the by ~90% of risk (cumulative rate (cSCC) thatfrequentlymetastasiseresultinginahighmortality sed bythe onset ofaggressive cutaneous squamous cell carcinomas 1 INSERM UMR er MAGEC), Saint-LouisHospital,ParisFrance, Genodermatoses (“MaladiesGénétiquesàExpression Cutanée”, Hovnanian UMR Imagine Institute, Laboratoryofgenetic skin diseases,INSERM 1 = , 2 , Sylvain Hanein 2/11) on proliferation and clonogenicity of RDEB cSCCKs. 1163 , F- 3 1 Imagine Institute,Translational GeneticsPlatform, , 2 , 75 5 1 , Matthias Titeux 0 1163 15 , Paris,France , , F- 3 , Rose Boudan 75 0 15 p , Paris,France

= =

0.03, Mann-Whitney) in the same the in Mann-Whitney) 0.03, 7/11) was inhibited upon inhibition 1 , Claire Barbieux 4 , Emmanuelle Bourrat 2 Université de Paris, = in vivo. RNA sequen 2/11) orhavenoeffect 4 Reference Centre for 5 Department ofGe- 1 , Sonia Gauch- 4 = , Alain 0.01, - - - - - covered with scales, crusts and milia involving the scalp, ears and shins. Anonychia waspresentsinceearlychildhood.Labora scalp, the involving milia and crusts scales, with covered plaques and papules lichenified erythematous pruritic extremely with ahistoryofblistersanderosionssincebirthassociated 1 understanding ofthepathogenesisSCCinRDEB. our expand can which aggressiveness, tumor with associated be identified various molecular alterations, some of which appear to on 383targeted cancer-related genesincSCCofRDEBpatients process. naling pathwaysrelatedtotheepithelial-mesenchymaltransition dose of dupilumab followed by 300 mg every two weeks. Patient loading mg 600 a administered was She therapies. systemic and ctions. No significant improvement was evident with many topical complained aboutpersistentitch interferingwithalldailyfun the COL7A1geneestablishing the diagnosisofEBP. The patient in mutations heterozygous two identified testing Genetic levels. tory workuprevealedmildeosinophilia andmildlyelevatedIgE mab. Here wereportacaseofEBP successfullytreatedwith dupilu EBP. with patients benefit possibly may it that suggesting PN, and pruritus generalized of treatment the for effective be to shown been has for dupilumab treatment AD, pathogenesis ofatopicdermatitis(AD).Besidesbeinganeffective the in role important an play which IL-13, and IL-4 cytokines: 2 type two by shared subunit receptor a (IL-4Rα), alpha receptor humanized monoclonalantibodytargeting theinterleukin(IL)-4 tions uniquetoEBP arenotfullyunderstood.Dupilumabisa lesions. The pathomechanisms underlyingtheclinicalmanifesta pruritus, prurigo nodularis (PN) and lichen simplex chronicus-like induced skin fragility, milia, nail dystrophy), EBP features severe collagen VII. InadditiontousualmanifestationsofDEB(trauma- terozygous orbiallelicmutationsinthegeneCOL7A1encoding recessive) dystrophic epidermolysis bullosa (DEB) caused by he (EBP) isararesubtypeofautosomaldominant(orlesscommonly Introduction &objectives:Epidermolysis bullosapruriginosa 2 Waseem Shehadeh DUPILUMAB PRURIGINOSA-ASSOCIATEDWITH PRURITUS TREATMENT OF EPIDERMOLYSIS BULLOSA P130 genes specifically in the tumors of the two patients who died who from metastaticsSCC.Someofthesemutationsmayimpactsig patients two the of tumors the in specifically genes serine/threonine kinase. We alsofound39additionalmutated to cell cycle, immune system, gene expression transcription, and Mutated geneswereinparticularinvolvedpathwaysrelated as well ascopy number variants ofcancer associated genes. We mutations deleterious recurrent with genes 57 identified also (signature 7)and APOBEC (signature2)aspreviouslyreported. alterations ultraviolet to related signatures mutational identified one orseveralcSCCwithoutmetastasisandarestillalive. We developed patients 7 whereas cSCC, metastatic and aggressive 52 yearsold(averageage32years). Two patientsdiedfroman patients (4menand5women).Patients’ agerangedfrom18to Genomic analyseswereperformedon16cSCCfrom9RDEB R-package. DeconstructSig the using identified were in-house developedPolyquerysoftware and mutational signatures variant calling.Drivermutationsearchwasperformedwiththe biopsies fromeachpatienttoexcludegermlinealterationsor appliedtobothtumoralandnon-tumoralskin was sequencing using a next-generation sequencing (NGS) custom panel. Panel for pathogenicvariantsin383epithelialcancer-related genes searched we patients, RDEB in carcinogenesis skin in involved patients. Liat Samuelov Sackler FacultyofMedicine,Tel-Aviv University, Tel Aviv, Israel Division ofDermatology, Tel-Aviv SouraskyMedicalCenter, Results: Taken together, the NGS approach based approach NGS the Takentogether,Conclusions: Materials &methods:To investigatethemechanisms An otherwisehealthy52-year-old femalepresented 1 1 , OferSarig 1 , JonathanBar Acta DermVenereol Suppl220 Materials & methods: 1 , EliSprecher Posters Results: 1,2 77 ------, Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta tas Sebelas Maret/Dr. Moewardi Hospital, Surakarta, Wibawa Yogyakarta Medicine Public Health andNursing,UniversitasGadjahMada, disciplines, in our case, we managed the patient together with surgery andoro-dentaldepartment. together patient the managed we case, our in disciplines, various involving treatment comprehensive to leading organs, as a reliable supporting diagnostic tool. KS can manifest in many resources setting, clinical matrix diagnostic tool can be considered limited the in Therefore, KS. for tool diagnostic standard the as genotyping and examination immunofluorescence have not do KS wasestablishedwithclinicalmatrixdiagnostictoolsincewe of diagnosis definitive the case, our no longer dry.In Conclusions: was skin His SPF30. sunscreen and emollient topical with with scallingandkeepinggoodoralhygiene.Hisskinwastreated no urinating problem. Oral and dental problems were managed surgery,later.of months was year two there one improved After problems urinating his and performed, were urethrotomy and was supportedbyclinicalmatrixdiagnostictool.Meatotomy which syndrome, Kindler’s for suggested hematoxylin-eosin occlusion suspectedforurethralandmeatalstenosis.Biopsywith and buccalulcers.Uretrographydemonstratedurethralexternal atrophy onhandsandfeet.Oralexaminationshowedcalculusteeth skin paper” “cigarette and xeroderma, legs, and neck face, his Results: appeared onhisleftcalf.Bothparentsarenotconsanguineous. fluid reddish containing blister later, days two scaled, was skin year.last delivery,normal with aterm born was He his somehow seven yearsold.Healsohadaninguinalherniaandwasremoved since hewastwoyearsoldbutcompletelyhealed when hewas in swallowing.Hehadbeensuffering fromintermittentblisters his dryskin.Healsosuffered fromrecurrentsoremouthandpain days beforehospitaladmission. There areblackishpatcheson pain duringurination;theseconditionsdevelopedforaboutthree and retention urine with came boy old 10-years & methods:A meatal and urethral stenosis affecting a 10-year old boy. hernia, inguinal ulcer oral with KS a reported, be to one first the reported in many case studies. However, in Indonesia, our case is riations. The multiple mucousinvolvementsinKShavebeen of mechano-bullous disorder with a broad range of clinical va spectrum a bullosa, epidermolysis of part a is syndrome Kindler involvement. mucous and inflammation, photosensitivity,colon atrophy, blisters, by characterized disorder recessive tosomal Introduction &objectives:Kindlersyndrome(KS)isanau Suci Widhiati DAN UROLOGY INVOLVEMENTS KINDLER SYNDROME WITH ORAL,INTESTINAL P131 the therapeuticpotentialofdupilumabinEBP. mechanisms. Larger and controlled studies are needed to confirm the presentedcasesuggeststhatEBP isdrivenby Th2-immune in improvement clinical significant and dysregulation. rapid The associated withEBP (andDEB)hasbeenattributedtoimmune at 12weeksoftreatment.Conclusions: The disablingpruritus and Scarring Index (EBDASI)alsorevealed aslightimprovement Disease Bullosa Activity Epidermolysis The lichenification. and of plaques and significant improvement in redness, scales, crusts with progressive improvement noticed at 12 weeks with flattening skin examrevealedmarkedimprovementat4-weeksfollowup analogue scale (VAS) forpruritus and astandard DLQIscores.Her visual a using life of quality and pruritus in improvement ficant evaluation at4weeksand12oftreatmentrevealedsigni 78 1 Hospital, Universitas SebelasMaret, Surakarta/Dr. Moewardi General Department DermatologyandVenereology Faculty of Medicine 2,3 EB2020 1 Dermatological examinationrevealedpoikilodermaon DewajaniPurnomosari 2 Departement Urology Faculty of Medicine Universi- 1 , Willa Damayanti st WorldCongressonEpidermolysisBullosa 1 , Wibisono 2,3 , Hardyanto Soebono 2 , IndahJulianto 3 Faculty of Materials Materials 2,3 1 , Tri - - - blepharitis (50.8%, with 42.6% achieving 20/20. Slit lamp examination demonstrated severe (23+/100). Best-corrected visual acuity was 20/60 in 57.4%, Sydney, Australia as seenintheprevioustworeports. disease, the of variant milder a with associated be may mutation report of this mutation in the indian context, and third overall. This first the is This loci. different two in substitutions Gly-Arg with variant is related to a particular genotype, and it has been reported variant. There isanongoingdebateonwhetherthis phenotypic in thepast-andoncereportedassociatedwithalbopapuloid twice only reported been has which G2064R, gene, COL7A1 lary dermalsclerosis.Geneticanalysisshowedamutationinthe papil and infiltrate minimal with cleft subepidermal a revealed examination ofthevesicleaswellalbopapuloidlesions cavity andothermucosaewereuninvolved.Histopathological over one leg, which had not been noticed by the patient. The oral the Pasinivariantofdisease. There weretwosmallvesicles upper back, consistent with the albopapuloid lesions described in bilateral feet, legs, Thighs and lower abdomen, with few over mid of milia. There weremultipleatrophichypopigmentedscarsover absence conspicuous atrophy,with and hyperpigmentation with to 3 cm diameter, especially around the ankle joints. These healed 0.5 from ranging healing, of phases various in erosions irregular There was no family history. On examination, we noted multiple proximally over bilateral legs, thighs and waistband area of trunk. spontaneous hypopigmented atrophic scars which progressed and atrophy(nomilia). At 4yearsofagehestarteddeveloping mities since1yearofagewhichhealedwithhyperpigmentation Indian childwithhistoryoftransientbullouslesionsoverextre Results: All IndiainstituteofMedicalSciences,Delhi, Pankhuri Dudani,NeetuBhari WITH RAREDE-NOVO G2064RMUTATION BULLOSA WITH ALBOPAPULOID LESIONS- DYSTROPHIC DOMINANT EPIDERMOLYSIS P132 questionnaire, slit lamp, and tear-film examination. and lamp, slit questionnaire, a standardised protocol, including an Ocular Surface Disease Index underwent a comprehensive ophthalmic examination according to centre andthe Australasian registriesofEBand AIBD. Participants histopathology wererecruited from a Dermatology subspecialty by confirmed diagnoses with patients 61 of study observational sian cohort. Materials & methods: the rangeandseverityofocularmanifestationsinan Australa examine prospectively to in AIBD second and EB in study first mucocutaneous lesionsinvolvingtheocularsurface. This isthe group ofchronicblisteringdermatosesthatareassociatedwith and Autoimmune BlisteringDiseases(AIBD)areaheterogeneous Introduction &objectives:InheritedEpidermolysisBullosa(EB) Brendon W.H. Lee AND AUTOIMMUNE BLISTERINGDISEASES INVOLVEMENT INEPIDERMOLYSIS BULLOSA PROSPECTIVE STUDY OF OCULAR DRY EYEDISEASEIDENTIFIEDIN A P133 was 13.63 (range Dry EyeDisease. The mean Ocular Surface DiseaseIndexscore Fifty-seven patients (93.4%) exhibited one or more symptoms of eyes of 61 patients (female 1 tal, Sydney,tal, Australia Minas T. Coroneo tralia Faculty of Medicine, University of NewSouthWales, Sydney, Aus- 2 Department ofOphthalmology, Prince of Wales Hospital, We are describing a case report of a 10 year old male old year 10 a of report case a describing are We

= 1,2 1,2,3 3

0-100) with 24.6% of patients graded moderate- Department ofDermatology, StGeorge Hospi- , DedeeF. Murrell n , Jeremy Tan =

62), conjunctival/corneal scarring (20.5%, = 54.1%), aged 2-88, were examined. 2 , MelissaRadjenovic Prospective, cross-sectional, Prospective, 1,3 Results: 3 , LienTat 122 2 - - - , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV on April 20, 2018. However, it took 1.5 years before embarking before years 1.5 took However,it 2018. 20, on April clarified. is status genetic its until (cryopreservation) frozen is embryo the procedure, quick ces fortheembryo!Sincegenetic diagnosisofDEBisnota analyze itsDNA. This proceduredoesnothaveany consequen day,and 3rd obtain to performed is biopsy” “embryo so-called a transfer is delayed until their genotype is clarified. Usually, on the expected. But if genetic diagnosis of embryos is necessary, embryo 1-2 embryosintotheuterinecavityofawomanandpregnancy is of an embryo, which usually lasts up to 5 days and the transfer of is theinvitro fertilizationprocedure. The nextisthecultivation test systemforexamininganembryoinaparticularfamily. Next thedevelopmentofanoftenindividualgenetic is preparatory stage in thefamilyanddeterminetheirparenthood. The nextimportant mutations causative specific the determine to order in family the is mandatorytoconductacomprehensivegeneticscreeningof it (PGD), diagnosis genetic preimplantation with IVF For DEB. body ofawoman. Thus guaranteeingthebirthofachildwithout the to transferring before mutation pathogenic a from “free” embryo an choose can we that means which diagnosis), genetic tic analysisanddeterminationoftheirgenotypes(preimplantation which youcangetacertainnumberofembryosavailableforgene family.the with in tool disease a genetic is a IVF of case, this In itself doesnotguaranteethebirthofahealthychildinevent of a healthy child may be considered. Of course, he IVF procedure the selectionofanembryowithoutageneticmutationforbirth risk. For such families, the question of using an IVF procedure with of having a sick child is 25% for each pregnancy, which is a high In the case of a sick child in a family with DEB, the repeated risk children withEBtocometheirdreamtrue.Materials&methods: bullosa andauniqueopportunityforcoupleswhohavealready epidermolysis of field the in Russia for study experimental an is receive suchaserviceinstandardstatemedicalinstitutions. This and implemented byDEBRA Russiaforthose families whocannot motherhood. IVFforparentsofEBpatientsprojectwasinitiated hope andachanceforhappiness-toknow the worldofanother DEB, with child a has already who woman a give to - 2 Mission genetic mutationincouples-carriersoftheEB. a without child healthy a of birth the - 1 Mission missions: two to givebirthahealthybabywithoutgeneticmutation. We had epidermolysis bullosa and a high risk of having a sick child again, is to give an opportunity to couples having children with dystrophic Laboratory andaMotherChildClinic. The aimoftheproject of DEBRA RussiawiththeparticipationofaGeneticResearch project implemented with the organizational and financial support Introduction &objectives:IVFforparentsofEBpatients-isapilot Genetico®, DEBRA Russia V. Kaimonov, V. Gnetetskaya Zhikrivetskaya, I. Kotov, Y. Kozlova,E.Musatove,Yu. Grigorieva, J. Kotalevskaya, T. Volgunova, E. Pomerantseva, A. Isaev, S. IVF FORPARENTS OF EBPATIENTS P134 multidisciplinary managementofEB. for ophthalmologicalevaluationshouldbeanintegralpartofthe life, risk of scarring, and subsequent visual impairment. Referral of ocularmanifestationsandtheirnegativeeffect onqualityof potential the of aware be should dermatologists paediatric age, and objectiveassessment.GivenEBmanifestsatbirthorearly patient-reported symptoms, Ocular Surface Disease Index score, on EB in found was Disease Eye Dry of finding novel Asions: trichiasis (5.7%, n and 59.4% had elevated tear osmolarity (>308mOsm/l). staining corneal significant exhibited 57.9% Furthermore, test. reduced tear break-up time and 92.4% had an abnormal Schirmer’s a had tested patients of 95.1% substantial; was dysfunction film = 25), limbal broadening (17.2%), symblepharon (8.2%, n = 7), and ectropion/entropion (3.3%, Results: The project was launched n 4). Tear= 4). Conclu n = 10), 10), - - - Santa Catarina,Brazil, Mullins collected usingsurveys.Results: All pilotsitesweregiventhesame instructionsandfeedbackwas accepted. 2 only approached, professionals healthcare 23 of out infographics werepilotedfor 3 months in 1 clinicalsiteinBrazil; across a total of 7 clinical sites. From July 2019, the Portuguese EB for 3 months in India, New Zealand, Brazil, Chile, and Columbia teams (Spain, UK). From June 2019, the English draft was piloted India, New Zealand, Austria, Australia, Spain) including 2 nursing from a multidisciplinary team of 8 international EB experts (UK, EB experts’ experiences in LRS. Advice and reviews were obtained Portuguese withsupportingevidencefrom3publishedCPGsand Body and Skin: EB Infographics” were developed in English and Study,Do, “Plan, the Using Health “The approach, cycles1” Act with considerationsforLRSalternatives.Materials&methods: guidelines (CPGs), to present evidence in a clear and simple way practice clinical to linked infographics, for were objectives The into practiceisexacerbatedinrareconditionssuchasEBLRS. burdens LRShealthsystems. The challengeofputtingevidence that theevidence/practicemismatchindevelopingcountries into practiceinLRS. The World HealthOrganisation recognises a DEBRA group.EBWBisnotaloneinstrivingtobringevidence help EB patients, their families, and doctors in countries without initiated aprogramme todevelop EB infographics forLRSto The DEBRA InternationalEB Without Borders(EBWB)team clinical guidancefordailycareinlow-resourcesettings(LRS). condition affecting the skin and various bodyparts with little Introduction &objectives:Epidermolysisbullosa(EB)isarare Kattya M.Mayre-Chilton CARE INLOW-RESOURCE SETTINGS INFOGRAPHICS FOREPIDERMOLYSIS BULLOSA DEVELOPING EVIDENCE-BASED P135 1 love forchildren. This isthe projectaboutlife. The couragetojustdream. This is aprojectaboutlove... courage toallowyourselfdreamaboutanothermotherhood. The society. from misunderstanding the despite forward, go to EB whoneedsaspecialapproachandlotoftime. The courage to pay sufficient attention to both a newborn and a sick child with that amistake mayoccur andachild with EBwill be born.Courage take risks without confidence in the result. The courage to accept project aboutunlimitedcourage. The couragetotakeastepand the patientgavebirthtoahealthygirl!Conclusions: This isthe 2019, 14, September on and procedure, IVF the underwent she 2018, 27, December On 2018. December early in IVF for quota a received project, the of stages all and examinations of series a passed having patient, second A2019. November of end the at known be will which of results the PGD, with IVF undergo will patient the November On 2019. July in only received was quota treatment before the IVF procedure, in connection with which the and giving birth to a child. The first patient underwent long-term comprehensive measures to prepare a woman’s bodyforreplanting is obtainingaquotaandimplementinglongstageofconducting test systemforexamininganembryoinaparticularfamily. Next preparatory stagewasthedevelopmentofanindividualgenetic this familyanddeterminetheirparenthood. The nextimportant genetic examination to determine specific causative mutations in comprehensive preliminary a underwent families the Then, EB. are mothersofchildrenwithsevererecessivedystrophicform women Both criteria. necessary the account into taking project, families fromdifferent citieswereselectedtoparticipateinthe on theprojecttoresolvealllegalandbureaucraticissues.2 Hospitals NHSFoundationTrust, London,UK, Zealand DEBRA International,Vienna, Austria, 1 4 1,2 DEBRA NewZealand,Wellington, New , Lie A. Taguchi 3 sitesfoundusinginfographics Acta DermVenereol Suppl220 2 1,3 Guy’sand StThomas’ , LeaPrujean 3 Posters DEBRA Brasil, 4 , Olivia 79 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Brazil female, EBDR diagnosed with carcinoma, with right lower limb lower right with carcinoma, with diagnosed EBDR female, old, years R.C.P,39 03: Cases days. 5 for occluded remaining cover, secondary as dressing absorbent an and blisters and skin transfer foamwasstartedasprimary coveroftheareaswithout every 48hoursafteranimmersion bath. The useofsoftsilicone used were Dressings buttocks. and elbows neck, hands, body: was absenceofskinonlegsandblistersinotherregionsthe Congenital CutisandEpidermolysisBullosasincebirth. There 02: A.T.S.,2Case process. Years, healing female, the Aplasia of Dressings were changed every 2 days, resulting in an improvement soft siliconetransferfoamcoverandbidirectionaltubularmesh. a of application by followed solution, saline 0.9% with cleansed were lesions the follow-up, During response. positive a without dressings hydrofiber and foam absorbent gel silicone used had lesions intherightandleftlowerlimbs.Foulsmellingodour. She Female, 2 years old, dystrophic bullous epidermolysis, presenting dressing. the of efficacy the evaluate follow-up forms and photographs of the lesions were used to transfer foamdressingstotreatwoundsandskinlesions.Home different periodsoftheyear. All thepatientsusedsoftsilicone in 2019, in Brazil in treated cases Bullosa Epidermolysis three study.Reporting descriptive series, Materials &methods:Case foam dressingsintreatingpatientswithepidermolysisbullosa. transfer silicone soft of effectiveness the Evaluate Objective: matic softsiliconedressingsandoutcomesrecordedonfollowup. atrau with treated were patients complications, prevent to need mutation. Duetothecomplexityoftreatingtheselesionsand involved and level, cleavage distribution, involvement hology, that are subdivided according to inheritance pattern, lesion morp sometimes inthemucousmembranes. There arefourmain groups characterized bythetendencytoproducevesiclesinskinand diseases of group a includes that dermatosis hereditary rare, a as Introduction &objectives: Bullous epidermolysis (EB) is defined 1 Mirelly Mendes, Luciana EPIDERMOLYSIS BULLOSA:CASESERIES SILICONE TRANSFER FOAM DRESSINGSIN EFFICACY OF ATRAUMATIC SOFT P136 “The HealthBodyandSkin:EBInfographics”(n Table 1.DemographicsoftheEBsubtypesaccessingpilotsitesandthosewhoweregiven for infographics implementation in2020. EB the finalise to month 1 over Spanish and Portuguese, English, in feedback Community EB direct collate translation ofinfographicsbeconsidered.Ournextstepsareto further suggests evidence The beliefs. and cultures, languages, and veryuseful.Conclusions:LRSarechallengedbynumerous them liking mainly to use of fear and inaccuracies, confusing, to languagemisunderstanding.Feedbackonbathsrangedfrom from the saline bath, baths were summarily stopped. This was due (1%) EB patient from India, out of 93, reported blisters resulting Other languagesrequestedincludedSpanishandHindi.Only1 in their mother-tongue appropriate (2in English; 1in Portuguese). 80 tive, Representative, Cobermed® Brazil, JEB EBS Language KS DDEB Other RDEB Total WOCN Nurse,Sales Manager, 3 WOCN Nurse,SalesRepresentative, 4

EB2020 1 18 40 N°of EBpatientsseen English 4 24 6 63 155 1 st , Pinheiro, Suyanne WorldCongressonEpidermolysisBullosa 8 19 Infographics N° giventheEB 4 14 3 40 88 2 WOCN Nurse,Sales Representa- = 93/160;58%) 1,2,3 2 , Duque,Carla Mölnlycke® Health Care Results: 1 N°of EBpatientsseen Portuguese 4 5 4 WOCN Nurse,Sales Case 01: IAS, 01: Case 3 , Carmen, 1 Infographics N° giventheEB 4 5 - - this work Public Health,USA Center,Tehran University of Medical Sciences, Iran, Institute of Dermatology, King’s College, UK, Iran, School ofMedicine, USA Biology, ThomasJefferson University, USA, University of Medical Sciences, Iran Sani 1 Hannah Mumber, Bs SIMPLEX: NAXOSDISEASE IN THE FORMOF EPIDERMOLYSIS BULLOSA CARDIOMYOPATHY AND SKINFRAGILITY RIGHT VENTRICULAR ARRHYTHMOGENIC BIALLELIC JUP MUTATION INFAMILIES WITH P137 maintains theintegrityofinjuryedge. and is effective in promoting healing without trauma or pain and lesions the of area exposed the improving considerably bullosa, effective andsafeforthetreatmentofpatientswithepidermolysis sions: These casessuggestthatsoftsiliconetransferfoamuseis heart rate variability in Holter-monitoring, while the older patient or significant family history. The younger patient showed reduced in relationtoage.Neitherofthem showedanycardiacsymptoms tion allowedustostudytheprogression ofcardiacinvolvements 2.5 year old and a 22-year-old, with the same homozygous muta microscopy displayed hypoplastic desmosomes. Two probands, a electron ultrastructure and epidermis, the in plakoglobin of lack the showed Immunofluorescence controls. versus patient the in the highlydown-regulatedgeneamong21EB-relatedgenes homozygosity.Whole-transcriptome sequencingbyRNA-SeqrevealedJUP as of region a of Mb 10.7 within disclosed was JUP:c.201delC;p.S68Afs*92 in mutation homozygous biallelic unreported previously a EBS, with presenting families unrelated levels. ultrastructural and tissue both at profiling consequences ofthemutationweredeterminedbyexpression well aswithwhole-transcriptomeandexomesequencing. The mutations withatargeted next-generationsequencingpanelas epidermolysis bullosa (EB)syndromes forunderlying genetic & methods: We examined alarge cohortof362familieswith expression in NXD has not been completely established. Materials variable and onset, of age penetrance, disease regarding lations loss-of-function mutationsinJUP. Genotype-phenotypecorre and woollyhair. Ithasbeenpreviouslyassociatedwithbiallelic epidermolysis bullosa simplex (EBS), palmoplantar keratoderma, with skin abnormalities including skin fragility in the form of arrhythmogenic rightventricularcardiomyopathy(ARVC) along Introduction & objectives: Naxos disease (NXD) presents with ical and Research Center Iran, had, PhD UK, Niaziorimi, MSc was performed every 2 days, for a period of 2 months. 2 of period a for days, 2 every performed was soft silicone exudate transfer foam was applied. Dressing change was debridedandsubsequentlytreatmentwithsilversulfate exudate, adhered necrosis and a fetid odor. On 03-06-19, the lesion lesion. The lesionpresentedabedwithlarge amountofserous ci nejad-Najmabadi Pathology & Genetics Center, Iran, Ariana Kariminejad, MD Nikoo Mozafari, MD deh, MD Beheshti UniversityofMedicalSciences,Iran, University, USA, Jefferson Institute of MolecularMedicine, Jefferson Thomas 13 , Jouni Uitto, MD, PhD 9 11 , LuLiu,PhD Kawsar Human GeneticsResearchKawsar Center, Iran, 7 , F. Rajabi,MD ,1,2,3 5 Tehran UniversityofMedical Sciences, Iran, , Leila Youssefian,Leila MSc , 1 , 2 , Fahimeh. Abdollahimajd, MD 2 Department of Dermatology and Cutaneous 10 , Alyson Guy, MSc 1,2,14,# 6 , Amir Hossein Saeidian, MSc 6 15 12 , Z.LiaosadatMirsafaei,MD ; Anjali Rajan ; Anjali NewYork University College of Global , John A. McGrath,MD,FRCP, FMedS- 1,2 . # Both authors contributed equally to 10 Viapath, St Thomas’ Hospital, 1,2,4,5 9 Rajaei Cardiovascular Med- 10 , M.Faghankhani, MD 1,2,15,# , Sirous Zeinali,PhD ; Hasssan Vahidnez; Hasssan - 3 14 7 Pasteur Institute of Children’sMedical Boston University 6 , Soheila Sotou- Results: 8 1,2,4 Mazandaran 8 , Alizadeh- 13 , Fatemeh 12 St John’s Conclu Karimi- 6 Shahid In two 3,11 1,2 - - - , , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Melbourne, Parkville, VIC, Australia, Children’s Hospital, Parkville,VIC, Australia University, Parkville, VIC, Australia, in Convergent Bio-NanoScience and Technology, MIPS,Monash Pang 1 University, Parkville, VIC, Australia, Monash Institute of Pharmaceutical Sciences (MIPS), Monash model ofdominantDEB(DDEB). These micecarryamutation recently usedCRISPRtechnologytoestablishanovelmouse pathogenesis andoptimaltreatmentarepoorlyunderstood. We its problem, clinical significant a being pain this Despite pain. (DEB) ischaracterizednotonlybyblisteringbutoftensevere Introduction &objectives:DystrophicEpidermolysisBullosa B.R.C. Smith DYSTROPHIC EPIDERMOLYSIS BULLOSA A NOVEL MOUSEMODEL OF DOMINANT TREATMENT OF EB-RELATED PAIN USING UNDERSTANDINGIMPROVING AND P138 valve involvementwithprogressiontowards ARVC. in JUP intwopatientswithconcomitantcutaneousandcardiac associate apreviouslyunreportedbiallelichomozygousmutation diagnosis. definite as categorized criteria possible ARVC diagnosis, and the older patient showed two major criteria, the younger patient had one major criteria categorized as of myocardial fibrosis was seen. Based on 2010 revised task force including myocardial thickness and wall motion, and no evidence the adult patient. It revealed normal size and function of chambers, resonance imagingwithandwithoutGadoliniumwasconductedin plore structural changes in early stages of ARVC, cardiac magnetic and pulmonary valve insufficiency in the younger patient. To ex displayed mild mitral andtricuspid regurgitation in both patients Echocardiography V3. and V2, V1, in waves Tinverted showed tal, Parkville, VIC, ville, VIC, Australia, ville, Genetics Theme,Murdoch Children’s Research Institute, Park- 1,2,6 1,2 , P.A.Shenoy 6 Department of Adolescent Medicine, Royal 2 Department ofPaediatrics, University of 3,4 , J.S. Kern 4 ARC Centre of Excellence 5 3 Royal MelbourneHospi- Drug Discovery Biology, 5 , N.A. Veldhuis Conclusions: we Thus, 3,4 , K.C. - compare theeffectiveness ofdifferent clinically-relevantanalge to used be can and patients, DEB in seen that to similar stimuli demonstrates anincreasedsensitivitytomechanicalandthermal which recapitulates the clinical features of DDEB seen in patients, mice. normalize the mechanical hypersensitivity of the Col7a1ΔG2037R at standardclinicaldosesbothdrugswereabletoonlypartially fectiveness of Meloxicam and Buprenorphine, and observed that ef the compared we Next, pain. DEB-related investigating for provides evidence that our mice are a clinically-relevant model and 2017), Brain, al, et Bischhoffshausen (von previously tients directly mirrorswhathasbeenobservedinrecessiveDEBpa sensitivity increased Importantly,this stimuli. heat and chanical me both to sensitivity pain increased significantly showed mice Results: lize the responses of Col7a1ΔG2037R mice in the von Frey assay. and to help develop more effective treatments forEB-related pain. understand the underlying pathophysiology of DEB-related pain better to model this use to plan we forward, Moving agents. sic (Buprenorphine) –wastestedbycomparingtheirabilitytonorma a non-steroidal anti-inflammatory drug (Meloxicam) and an opioid Subsequently, the effectiveness of different analgesics – including for hypersensitivitytomechanicalandheatstimulirespectively. assess that tests pain behavioural standardised are which assays, any visibleblisteringusingboththevonFreyandHargreaves mice andwild-typelittermateswerecomparedintheabsenceof to treatEB-relatedpain.Materials&methods:Col7a1ΔG2037R assays andtocomparetheeffectiveness ofdrugscommonlyused behavioural pain-related standardised in mice Col7a1ΔG2037R aim ofthisprojectwastoestablishthebaselineresponsesour the pain, DEB-related treat and understand better Tostability. thermal COL7A1 reduced and microscopy, electron via fibrils anchoring abnormal immunostaining, via expression protein blistering as well as nail and digit loss over time, reduced COL7A1 Like DDEB patients, the mice display mild, dominantly-inherited (ΔG2043R). patients in DDEB for responsible commonly most that to corresponds directly that (ΔG2037R) Col7a1 mouse in Our novel Col7a1ΔG2037R mouse model, mouse Col7a1ΔG2037R novel Our Conclusions: In the absence of any visible blistering, Col7a1ΔG2037R Acta DermVenereol Suppl220 Posters 81 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta Greenblatt, Danielle21 Graaf, Petrade27 Geuens, Sam26 Gerner, Erik22 G Fletcher, Godfrey22,26 Fearon, Jimmy23 F Escámez, MaríaJosé6 Eming, Sabine5 E Dieter, Kathrin15 Dasgeb, Bahar21 D Curry, Joe17 Crombie, Catriona16 Collins, Sharmila15 Chan, Jennifer27 Calvo, Margarita 20 C Bunting, Simone26 Bruckner-Tuderman, Leena5 Bruckner, Anna 10,1719 Brackman, Gilles22 Bodemer, Christine21 Bernardis, Catina18 Bauer, Johann5,14,17 Baertschi, Michael18 B Albert, David17 Akker, PeterC.vanden13 Abraham, David6 A By pagenumber SPEAKERS - Jessop, N;(P42),(P43) Jeffs, E;(P74),(P75) James, D;(P33),(P111) Jacków, J;(P115), (P117) (P58) Izmiryan, A; Hughley, E;(P99) Hubbard, L.D;(P19) Huang, C.H;(P9) Guttmann-Gruber, C;(P34) Graham, T;(P45) Gorell, E.S;(P29) Gorell, E;(P124) Gewert, S;(P125) Fuentes, I;(P48) (P73) Filoni, A; Elsadat, H;(P127) Dudani, P;(P132) Drislane, C.A;(P96) Delgado-Miguel, C;(P56),(P102),(P94) Dayal, J.H.S;(P128) Chottianchaiwat, S;(P17),(P22) Chen, V.M; (P107),(P109) Chang, C.C;(P80),(P87) Chacón-Solano, E;(P112) Cases, I;(P66),(P67) Cao, Q;(P30) (P103) Bruckner; A.L; Brena, M;(P40),(P41) Box, R;(P54) Bonafont; (P81) Blom, K;(P37) Barritault, D;(P121) Barbier, M;(P7) Balatska, N;(P20) Baardman, R;(P104) Augsburger, B.D;(P12) (P39) Alheggi, A; Alharthi, R;(P85) P numbersrelatetoposternumber AUTHORS INDEX(POSTERS– 82 Author Index , 25 Abstracts oforalpresentations , 27 , 816 by firstauthor) Ott, Hagen20 O Nyström, Alexander 7 N Murrell, DedeeF. 9,15 Mellerio, JemimaE9 Mellerio, Jemima8 McGrath, John5 Mayre-Chilton, Kattya26 Martinez, Anna E.16,24 Marinkovich, M.Peter13 Makow, EvaninaMorcillo23 Magin, Thomas M.9 M Lwin, Su11,23 Larcher, Fernando11 Lara-Corrales, Irene18 Lane, Alfred 17 L Krishnan, Suma15 Krämer, SusanneMarie18,28 Kopelan, Brett15 Koller, Ulrich13 Kitzmüller, Sophie16 Kiritsi, Dimitra7 K Hund, Michael22 Hubbard, Lynne 27 Hovnanian, Alain 12 Hirschfeld, Josefine6 Hiremagalore, Ravi21 Has, Cristina5,16 Harrington, KevinJ.7 Harper, Natasha26 H Parvizi, M.M;(P110) O'Sullivan, M;(P93) (P15) Onoufriadis, A; Ogboli, M;(P59) O’Sullivan, G.M;(P31),(P32) O’Haver, J;(P62) O’Connor, C;(P69) Natale, M;(P70) Mumber, H;(P137) (P61) Mughal, A.Z; Morisaka, H;(P86) Moore, M;(P122) Mendes, L;(P95),(P136) Mehta, N;(P120) Mayre-Chilton, K.M;(P83),(P135) Martínez-Santamaría, L;(P76) Marinkovich, M.P;(P52),(P123) Mariath, L.M;(P4) Malta, M.D;(P68) Makarova, S.G;(P13) Mahajan, T;(P65) Magno, J.A;(P97),(P101) Lu, S;(P2) Lim, C.E;(P78) Liat, S;(P25) Levin, L.E;(P91) Lee, S.J;(P105) Lee, B.W.H; (P133) Lara-Sáez, I;(P57) Lalosevic, J;(P14) Kotalevskaya, J;(P24) Kotalevskaya, J;(P134) Korolenkova, M;(P98) Kocher, T;(P16) (P38) Klausegger, A; Kiritsi, D;(P47) (P89) King, A; Jones, R;(P116) , 16232526 , 102024 , 1723 Zernikow, Boris20 Zambruno, Giovanna7 Z Woodley, David T. 9 V Uitto, Jouni5,12 U Torkington-Stokes, Rachel23 Tolar, Jakub10 Tang, Jean14 Tamai, Katsuto11 T Sumeray, Mark13,22 Sprecher, Eli17 Spellman, Mary14 South, Andrew 8 Smith, Gill18 Shabir, Assya 26 Schräder, Nicholas19 S Rotschein, Pavel19 Rosa, LauraDe12 Roop, Dennis11 Ried, Lena25 Reimer, Antonia 18 R Prodinger, Christine25 Price, Amy 27 Pope, Elena16 Podrebarac, Theresa 14 Plevey, Katie17 Petrof, Gabriela25 Perretti, Mauro16 P Zauner, R;(P23) Yubero, MaríaJoaoG;(P90) Yerlett, N;(P60) Xie, D;(P5) Wood, M;(P21) Wimmer, M;(P18) Widhiati, S;(P131) White, K;(P11) Wharton, S;(P126) Welponer, T;(P64) Valinotto, L;(P72) Tu, W.T; (P71),(P79) Teng; J;(P49) Teng, C.E;(P28) Tartaglia, G;(P44) Tanaka,(P114) A.C; Stevens, N.E;(P88) Snelson, K;(P6),(P46) Smith, G;(P63) Smith, BRC;(P138) Shehadeh, W;(P130) Shakouri, R;(P100) Shah Moksha,M;(P84) Sathishkumar, D;(P50),(P51) Salamon, G;(P55),(P119) Rogers, C.L;(P27) Robertson S.J;(P82) Ricart, S;(P108) (P26) Reimer, A; Ragot, H;(P129) Prodinger, C;(P3),(P10),(P92) Price, H.N;(P113) Pope, E;(P8) Plevey, K.E;(P1) Pillay, E.I;(P77) Phillips, G.S;(P53) Petrof, G;(P106) Pawlak, U;(P36)