ETAS_12 bullous

Bullous and Vesicular Dermatoses 417

12 Bullous and Vesicular Dermatoses

Christine J. Ko, MD

C o n t e n t s

12.1 Molecular Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .419

12.2 Microscopic Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421

12.3 Bullous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422

12.4 Diseases that Can Present with Bullae . . . . . . . . . . 429

12.5 Vesicular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430

12.6 Common Allergens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433

12.7 Plant Allergens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435

12.8 Tips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436

12.9 Plant Irritants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437


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12.1 MOLECULAR LEVEL

Figure 12-1.

Armadillo Family• Plaqueproteinsthatfunction inadhesion

• Includesbeta-catenin(plakoglobincansubstitute forbeta-catenin)inadherensjunctions

• Plakoglobin(85kDa)andplakophilinsindesmosomes

uTIPa Mutations: armadillo protein Disorder beta-catenin ........................................... 1.) some pilomatricomas

........................................................................ 2.) colorectal carcinoma

plakoglobin ............................................. Naxos disease

plakophilin 1 ............................................. ectodermal dysplasia with skin fragilityaAntigenic: armadillo protein Disorder plakoglobin ............................................. coprecipitates with desmogleins in pemphigus

........................................................................ foliaceus and pemphigus vulgaris

420 2011/2012DermatologyIn-Review l Committed to Your Future

Cadherins• Calcium-dependent adhesionmolecules

• Classic:E-cadherin, N-cadherin,P-cadherin

• Desmosomaltype(hashomologytoclassiccadherins):desmoglein1(160kDa),desmoglein3(130kDa),desmocollins

• Inadherensjunctionsand desmosomes

Enzymes• Transglutaminase 1: Mutatedinlamellarichthyosis• Transglutaminase 3:77kDa,theantigenfordermatitisherpetiformis

Integrins• Foundbetweencell membranesand basementmembrane infocalcontactsandhemidesmosomes

Intermediate Filaments(IF)• Foundwithinavarietyofcells,manydifferenttypes

• TypeI=acidickeratins9-20,chromosome17

• TypeII=basickeratins1-8,chromosome12• TypeIII=vimentin,glialfibrillaryacidicprotein(GFAP),desmin,peripherin

• TypeIV=neurofilaments• TypeV=nuclearlamins• TypeVI=nestin

Plakins• Plaqueproteinsthatfunctioninadhesion• DesmoplakinI(250kDa)andII(210kDa),envoplakin(210kDa),periplakin(190kDa)in

desmosomes• BullousPemphigoidAntigen1(BPAg1)(230kDa),plectin(500kDa)inhemidesmosomes

uTIPaMutations: cadherin Disorder desmoglein1 ........................................... striatepalmoplantarkeratoderma(PPK)type1 E-cadherin ............................................... gastriccanceraAntigenic: cadherin Disorder desmoglein1 ........................................... pemphigusfoliaceus desmoglein1 ........................................... Ritter’sdisease desmogleins1/3 ................................... mucocutaneouspemphigusvulgaris desmoglein3 ......................................... mucosalpemphigusvulgaris desmocollin ............................................. IgApemphigus

uTIPaMutations: integrin Disorder alpha-6-beta4-integrin ..................... junctional epidermolysis bullosa with pyloric atresiaaAntigenic: integrin Disorder beta4-integrin ........................................ ocular cicatricial pemphigoid

uTIPaMutations: IF Disorder keratin 1 ........................... ichthyosis hystrix keratins 1/10 .................. epidermolytic hyperkeratosis (EHK) .............................................. epidermal nevi with EHK keratins 1/16 .................. nonepidermolytic PPK keratin 2e........................ ichthyosis bullosa of Siemens keratins 3/12 ................. corneal dystrophy of Meesmann keratins 4/13 ................. white sponge nevus of Cannon keratins 5/14 ................. epidermolysis bullosa simplex variants keratins 6a/16 .............. pachyonychia congenita type 1 keratins 6b/17 .............. pachyonychia congenita type 2 keratin 9 .......................... epidermolytic PPK lamin a .............................. progeria


12.2 MICROSCOPIC LEVELAdherens Junction

• Mediatesquick,weakcell:celladhesion• ContainsE-cadherin,P-cadherin,alpha-andbeta-catenin,vinculinandradixin;alsoplakoglobin,likedesmosomes

• Importantincellsignaling;anchorsactinatinterfaceoftwocellmembranes

Desmosome• Mediatesslow,strongcell:celladhesion• Containsdesmosomalcadherins(desmoglein,desmocollin),desmocalmin(keratocalmin),desmoyokin,band6protein,plakophilin;containsplakoglobin,likeadherensjunctions

• Anchorskeratinintermediatefilamentsatinterfaceoftwocellmembranes

Focal Contact• Containsintegrins,vinculin• Anchorsactinatinterfaceofcellmembrane/basementmembrane

Gap Junction• Containsconnexins(makeupconnexons)• Allowsforcommunicationbetweencells

Hemidesmosome – Anchoring Filaments• Withinthebasalcell:BPAg1,plectin• Cellmembranespanners:alpha-6-beta4-integrin,BullousPemphigoidAntigen2(BPAg2=typeXVIIcollagen)(180kDa)

• Withinthelaminalucida:anchoringfilaments,laminin5(400-440kDa)

• Anchorskeratinintermediatefilamentsatcellmembrane/basementmembraneinterface

Lamina Densa• Containsentactin(nidogen)inacomplexwithcollagenIVandlamininandheparansulfate

Tight Junction• Containsoccludinsandclaudins• Importantinanintactskinbarrier(foundingranularlayer)

uTIPaAntigens Molecular Weights desmoglein 1 ........................................... 160 KDa desmoglein 3 ......................................... 130 KDa plakoglobin ............................................. 85 KDa BP Ag1 ........................................................ 230 KDa BP Ag 2 (collagen XVII) .................. 180 KDa desmoplakin I......................................... 250 KDa desmoplakin II ....................................... 210 KDa envoplakin ............................................... 210 KDa periplakin .................................................. 190 KDa plectin ......................................................... 500 KDa

uTIPaMutations: connexin Disorder 26 ................................................... 1.) Vohwinkel’s syndrome

.......................................................... 2.) KID syndrome

.......................................................... 3.) PPK with deafness

30.3, 31 ......................................... erythrokeratoderma variabilis

30 .................................................... hidrotic ectodermal dysplasia

uTIPaMutations: protein Disorder BPAg2 .........................................generalized atrophic benign EB laminin 5 .....................................JEB, Herlitz type plectin ..........................................EBS with muscular dystrophy alpha-6-beta4-integrin ...... junctional epidermolysis bullosa .........................................................with pyloric atresiaaAntigenic: protein Disorder BPAg1 and BPAg2-NC16A ....bullous pemphigoid BPAg2 ......................................... lichen planus pemphigoides part of BPAg2 ........................ linear IgA disease BPAg2-NC16A ........................herpes gestationis BPAg2-C terminal domain ....cicatricial pemphigoid laminin 5 .....................................cicatricial pemphigoid beta4-integrin .........................ocular cicatricial pemphigoid

uTIPaMutations: plakin Disorder desmoplakin ........................................... 1.) striate PPK ........................................................................ 2.) left ventricular cardiomyopathy ........................................................................ with woolly hair and striate PPK plectin ......................................................... EB with muscular dystrophyaAntigenic: plakin Disorder desmo-/envo-/peri-plakin, BPAg1 .... paraneoplastic pemphigus desmoplakin I and II ........................... Stevens-Johnson syndrome BPAg1 ......................................................... bullous pemphigoid


12.3 BULLOUS DISORDERSBullous Pemphigoid (BP)

• Clinical: Mostcommoninelderlypatients;tensebullae,noninflammatorybase,ruptureleadstowell-demarcateddenudedareasofskin;mayalsoseeurticarial,erythematousplaques;20%haveoralinvolvement;rarelyBP canbelocalizedtothevulvaortoaradiationsite;riskfactorsincludedementiaandParkinson’sdisease

• Histology:Subepidermalblisterwithmanyeosinophils;canhavecollectionsofeosinophilsindermalpapillae

• InurticarialstageofBP,interfacedermatitiscontainingmanyeosinophils• DIF: LinearbasementmembraneC3in~95%,IgG4in~80%;“n-serratedpattern”• IIF: (Idealsubstrate:salt-splitskin)linearatbasementmembranein70%• Abs:AgainstBPAg1,BPAg2-NC16Adomain

• BPAg2isthoughtpathogenic;neutrophilelastaseand/ormatrixmetalloproteinase-9(92kDagelatinase)cleavesBPAg2invitro

• Drug-induced BP: ClassicallycitedincitingdrugisLasix(furosemide),butsulfadrugsandthiol-containingdrugs(captopril,penicillamine,goldthiosulfate)maybemorecommon;othersareNSAIDS(ibuprofen,phenacetin),penicillinderivatives,cardiovasculardrugs(enalapril,nadolol,practolol);PUVAcanalsoleadtoBP

• Treatments: POsteroids,azathioprine,mycophenolatemofetil,nicotinamide,tetracycline

• TwootherdisorderscanpresentclinicallylikeBPbuthavedifferenttargetautoantigens,so-calledanti-p105andanti-p200pemphigoid

Chronic Bullous Disease of Childhood (CBDC)• Clinical:Childrenwithblistersincirculararrangementsonthegroin/lowerextremitiesandperioral/scalpareas;severepruritus

• Histology:Subepidermalbullaewithneutrophilsatthedermo-epidermaljunction;occasionaleosinophils

• DIF: LinearIgA• IIF: CirculatingIgAin~50%• Immunoelectron Mapping:IgAlocalizestothelaminalucidaandoccasionallyalsotothesublaminadensa

• Abs:Against97kDaantigenthatisapartofBPAg2• Treatments: Diseasetendstoresolvespontaneously,buttreatmentsincludedapsone,sulfapyridine,steroids

PEARL

w TenseBullae Bullouspemphigoid Epidermolysisbullosaacquisita Herpesgestationis

uTIPaImmunofluorescence Patterns • Bullous Pemphigoid – linear C3/1gG (epidermal side of split skin) • Herpes Gestationis – linear C3/lgG • Epidermolysis Bullosa Acquisita – linear lgG + others (dermal side of split skin) • Bullous Lupus Erythematusus – linear lgG + others • Porphyria Cutanea Tarda – multiple lgs, complement,

and/or fibrin at junction or around vessels • Cicatricial Pemphigoid – linear C3/lgG, sometimes lgA • Pemphigus – intercellular lgG/C3 • Dermatitis Herpetiformis – granular lgA • Linear lgA – linear lgA • CBDC – linear lgA


Cicatricial Pemphigoid (CP)• Clinical:Patientgenerallyolder,ages60-80;transientvesiclesthatresultinerosions/ulcersontheoralmucosainabout100%ofpatients;desquamativegingivitis;conjunctivainvolvedinabout70%andcanleadtoscarring/symblepharon/blindness;skinlesionsin25%(face/neck/scalp/groin/extremities)

• Histology:Subepithelialbullae,similartoBP• DIF: LinearC3,IgG,fibrinogen,occasionallyIgM/IgAatbasementmembranein90%

• IIF: linearatbasementmembranein20%• Drug-induced CP:SimilartoBP;sulfadrugs(sulfadoxine)andthiol-containingdrugs (captopril,penicillamine,goldthiosulfate)maybemostcommon;othersareNSAIDS(indomethacin),topicalmedicationsforglaucoma,penicillinderivatives,cardiovasculardrugs(practolol,clonidine),Lasix,5-fluorouracil

Dermatitis Herpetiformis (DH)(Duhring’sDisease)• Clinical: Oftenpatientsareinthe4thdecade,severelypruriticgroupedvesiclessymmetricallyonextensorsurfaces/occasionallyscalp;prurituscausesvesiclestobetransientasscratchingresultsinerosions;presentationcanalsobenonspecificwithpapules,urticaria,tensebullae,orpolymorphouslesions;spontaneousimprovementwithcyclicexacerbations

• Histology:Suprapapillaryvesicles,multilocular,containingmostlyneutrophils,papillarydermisandbasementmembranezonegetdestroyedduetoinflammatoryinfiltrate(nofestooning),reversefestooningontheroof

• DIF: Granular(rarelyfibrillar)IgA>C3indermalpapillaein100%• IIF: Negative• Abs: Againsttransglutaminase3;ELISAtestingcanbeorderedtocheckforantibodies

• Inceliacdisease,thereareoftencirculatinganti-endomysialandanti-gliadinantibodies• DDx: LinearIgA,DHsecondarytodrug,inflammatoryEBA,bullousSLE,BP,HG,erythemamultiforme

• Associations: HLADQ2(whichislinkedtothemorecommonlycitedHLAB8inacommonancestralhaplotype),thyroiddisease(40%),smallbowellymphoma(non-Hodgkin’slymphoma),90-100%haveabnormaljejunalbiopsies(similartoceliacspruepatients)butmostareasymptomaticintermsofceliacdisease

• Treatments:Gluten-freediet(gliadinisthesoluble,antigeniccomponentingluten)(rice,oats,cornareallowed),dapsone,sulfapyridone,sulfasalazine

Drug-Induced Pemphigus• Inducingdrugs:Thiol-containingdrugs(captopril,penicillamine,thiopronine)ordrugswithdisulfidebonds(gold,pyritinol);alsodrugsthathavethepotentialtoreleasesulfurmoieties(penicillins,piroxicam,cephalosporins),pyrazolonederivativesandenalapril(possiblysecondarytoanamidegroup),indocin,rifampin

uTIPa Abs against: • formwithmucosalandskinlesions:

BPAg2(distalC-terminaldomain) • ocularform:beta-4-integrin • formassociatedwithmalignancy:laminin5 (=epiligrin,BM600,kalinin,nicein)

PEARL

w Variant:Brunsting-Perrypemphigoid:nomucosal involvement,blistersonpatchesoferythemaonhead/neckwithscarring/scarringalopecia

w Treatments:Topical/intralesional/POsteroids,dapsone,cyclophosphamide,azathioprine


• 75%ormorelikepemphigusfoliaceus(especiallywhensecondarytothiol-drugs),25%resemblespemphigusvulgaris;pemphigusvulgaris-typemaybeincreasednowasnon-thiol-drugsareoftentheculprits

• DIF: 90%intercellular• IIF: 70%intercellular

Epidermolysis Bullosa (EB)• Clinical:InalltypesofEB,minormechanicaltraumaleadstoblisters,generallynon-inflamed,andhealingiswithorwithoutscarring/milia;naildystrophy/alopeciacanbepresentinalltypes(althoughlesscommoninsimplex)

• UittosuggestedclassifyingGABEBandEBsimplexwithmusculardystrophyas“hemidesmosomal”ratherthanjunctionalbasedonthemolecularlocalizationofdefectivegeneproducts,butthisisnotincommonclassifications

• Inheritance Tips: AllEBsimplexisautosomaldominantexceptforsomerarersubtypes(notlisted);“hemidesmosomal”andjunctionalEBareautosomalrecessive

Epidermolysis Bullosa Acquisita (EBA)• Clinical:ClassicallylikedystrophicEB,butinadults:noninflammatorytrauma-inducedbullae(oftenonhands/feet)thathealwithscarring/milia,increasedskinfragility;oral/esophagealinvolvementpossible(CP-like)

• NotethattheaboveistheclassicpresentationintheoriginalreportsofEBA;subsequently,BP-likepresentations(inflammatorybullae,ontrunk/extremities)havebeendescribed,andsomefeelthatEBAmaybeadiversegroupofdiseases

• Histology: Subepidermal,classicallynoninflammatory(PCT-likeordystrophicEB-like),butmaybeinflammatorywithneutrophils(DH-like)oreosinophils(BP-like)

• DIF: LinearIgG,(sometimesIgM,IgA,C3,fibrinogenaswell)atbasementmembranein100%;onbaseofsalt-splitskin(ratherthanroofforBP);“u-serratedpattern”

• IIF: IgGatbasementmembranein50%• Abs:AgainsttypeVIIcollagen(290kDa)• Treatments:Oftennon-satisfactory

MNEMONIC Subepidermal Split

PLAID

Pemphigoid (bullous)

Lupus(bullousSLE)

Acquisita(EBA)

IgA,linear Dermatitisherpetiformis

uTIPaImportant Subtypes Defects EBsimplex . . . . . . . . . . . . . . . . . . . . . . . . . keratin5/14

Weber-Cockayne

Koebner

Dowling-Meara(herpetiformis)aHemidesmosomal GeneralizedatrophicbenignEB . . . . . BPAg2

EBsimplexwithmusculardystrophy . . plectinaJunctional EB Herlitz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . laminin5

withpyloricatresia . . . . . . . . . . . . . . . . . . alpha6-beta4integrin

EBdystrophic . . . . . . . . . . . . . . . . . . . . . . collagenVII

PEARL

w Helpful Clinical Tips: Groupedblistersaremost commonlyseeninDowling-MearasubtypeofEBsimplex;enamelhypoplasiaismorecharacteristicofthejunctionalsubtypes;exuberantgranulationtissueperiorally/axillary/neckareaismostcharac-teristicoftheHerlitzsubtypeofjunctionalEB;thereisincreasedriskofSCCsintheHallopeau-SiemenstypeofrecessivedystrophicEB uTIP

a�ClumpedtonofilamentsareseenonelectronmicroscopyintheDowlingMearasubtypeofEBsimplex;recessivedystrophicEBissecondarytoaprematurestopcodonincollagenVII

PEARL

w Associations:Inflammatoryboweldisease,autoimmunedisorders(SLE,rheumatoidarthritis,diabetes,Hashimoto’sthyroiditis),amyloidosis


Epidermolytic Hyperkeratosis(BullousCongenitalIchthyosiformErythroderma)

• Clinical: Infantsareoftenbornoraffectedearlyonwithblistersthatresolve;subsequentlyaffectedpatientsdevelop“corrugated”layeredscalingthatisgeneralizedbutprominentoverflexuralareas

• Autosomaldominant,defectinkeratin1/10• Histology:“Epidermolytichyperkeratosis,”acharacteristicpatternofdegenerationofthecellsofthespinouslayer

Fogo Selvagem• Clinical:EndemicformofpemphigusfoliaceusinruralareasofBrazil,increasedincidenceinchildren/youngadults;flaccidbullaethatrapidlybecomesuperficialcrustederosionsthatcanlooklikeeczemaorpsoriasisorimpetigoorseborrhea;canbevegetativeorexfoliative;Nikolsky’ssignpositive

• Possiblythisisaninfectiousdiseasethatistransmittedbytheblackfly(Simulium)• Histology:Identicaltopemphigusfoliaceus• Antibodyprofileidenticaltopemphigusfoliaceus• Treatments: Steroids

Herpes Gestationis (HG)(PemphigoidGestationis)•Clinical: 1:50,000pregnancies;onsetinsecondorthirdtrimesterorpostpartumperiod;canrecurwithsubsequentpregnanciesorwithoralcontraceptiveuseormenstrualperiods;lesionsareurticarialpapules/plaquesaroundumbilicusthatprogresstotheabdomenandrestofbody;blistersareofteninacharacteristicannularorpolycyclicarrangement

• Neonate: Maybeprematureorbesmallforgestationalage;<5%willhavebullae• Histology: Subepidermalsplit;issimilartoBP• DIF: LinearC3,occasionallyIgGatbasementmembrane;in100%• IIF: Oftennegative;75%ofpatientshaveacirculatingHGfactor(anIgGantibodythatfixescomplement)

• Abs:AgainstBPAg2,sometimesBPAg1• Associations: Graves’disease,rarecasereportsofassociatedchoriocarcinoma,HLADR3andDR4

• Treatments:POsteroids

IgA Pemphigus• Clinical:Middle-aged/elderlypatients;subcornealpustulardermatosis(SPD)type:serpiginouspustules;intraepidermalneutrophilic(IEN)type:flaccidbullaethatcanstartasvesiculopustules,lesionsenlargeperipherally,causingannular“flower-like”arrangements;commonsitesareintertriginous;prurituscommon

• Histology:Subcornealorintraepidermal;neutrophilsinepidermis,noacantholysisobvious

• DIF: 100%intercellularIgA(distinguishesSPDtypefromsubcornealpustulardermatosisofSneddonandWilkinson),rareC3

• IIF: IntercellularIgAin50%

• Abs:AgainstdesmocollinsinSPDtype,sometimesdesmogleins

• Associations: IgAgammopathy• Treatments:Dapsone,steroids


Linear IgA Disease• Clinical:CanpresentlikeDHorBPwithurticariaandoral/conjunctivallesions;sometimeslesionsaremorelinear/annular/serpiginousascomparedtoBP;commonsitesareintertriginous;rarelyhasaTEN-likepresemtation

• Histology: SubepidermalblisterthatcanlooklikeDHwithneutrophilsalongthedermoepidermaljunction

• DIF: LinearIgAatbasementmembranein100%• IIF: LinearIgAatbasementmembranein20-70%• Abs:AgainstportionofBPAg2(linearIgAdiseaseantigen=LAD-1)(97kDa);notethatsomepatientsoriginallydescribedashavinglinearIgAwithantibodiesagainsttypeVIIcollagenmayactuallyhavehadEBA

• Drug-induced:Commonlyvancomycin,PCNs,cephalosporins,captopril;alsolithium,diclofenac,amiodarone,PUVA,Lasix,IL2,IFNgamma,phenytoin,atorvastatin,second-generationACE1,angiotensinreceptorblockers

• Treatments: Dapsone,steroids,otherimmunosuppressants

Paraneoplastic Pemphigus• Clinical:Canresemblesevereerythemamultiformewithterribleoralulcerationsorpemphigusvulgaris,oroccasionallybullousorcicatricialpemphigoid;skinlesionscanbepolymorphouswitherythematouspapules,lichenoidlesions,targetoidlesions,flaccidortensebullae;respiratoryfailurecanleadtodeath

• Histology: Suprabasilaracantholysisanddyskeratotickeratinocyteswithbasalvacuolarchange

• DIF: IgGandC3intercellularandlinear/granularatdermoepidermaljunction

• IIF: (Bestonratbladder)intercellularIgG• Abs:Againstplectin,desmoplakinI(250kDa)andII(210kDa),BPAg1,envoplakin,periplakin,170kDaantigen,desmoglein1and3

• Treatments:Thediseaseoccasionallyremitswithtreatmentofthetumor

Pemphigus Erythematosus (Senear-UsherSyndrome)• Clinical:Anoverlapoflupuserythematosusandpemphigusfoliaceuswitherythematouscrustsandhyperkeratoticlesionsandoccasionalbullaeonthenose/ears/cheeks/scalpandchest/extremities

• Histology:Likepemphigusfoliaceus• DIF: LikepemphigusfoliaceusandwithlinearIgGatdermoepidermaljunction• Lupusbandpositivein80%;ANApositivein30%• Treatments: PO/topicalsteroids,sunscreen

PEARL

w Criteria — Need 3 major or 2 major plus 2 minor Major Criteria 1.) Polymorphousmucocutaneouseruption 2.) Concurrentinternalneoplasia, 3.) Characteristicserumimmunomonunoprecipitationfindings Minor Criteria 1.) PositiveIIFonratbladder 2.) PositiveDIF 3.) Acantholysisonbiopsy

uTIPa Associations: Malignancy,especiallynon-Hodgkin’s

lymphoma(42%)chroniclymphocyticleukemia(CLL)(29%),Castleman’s(6%),sarcoma(6%), thymoma(6%)


Pemphigus Foliaceus (PF)• Clinical:Male:female1:1;meanage50-60;flaccid,superficialbullaethatruptureeasily(canlooklikeimpetigo)orlocalized/generalizedexfoliationwithcrustingandmalodor;Nikolsky’ssign-positive;endemicinTunisia

• Histology:Subcorneal/intragranularacantholysiswith“clingons”=acantholyticcellshangingontotheblisterroof;neutrophilscanbepresentinblistercavityandcanresembleimpetigohistologicallysocorrelatewithclinical

• DIF: IntercellularIgG4(maybemoreprominentinupperlayersofepidermis)• IIF: (Guineapigesophagusbest)intercellularin80%• Abs: Againstdesmoglein1• Notethatdesmoglein1ismutatedinstriatePPK• NotethatplakoglobinismutatedinNaxossyndrome(autosomalrecessivesyndromewithright-sidedcardiomyopathy,striatedPPK,woolyhair)

• NotethatdespiteseveralrecentcasereportsofneonateswithPF,neonatesarenotusuallybornwithPFdespitethefactthatmaternalautoantibodiesagainstdesmoglein1cancrosstheplacenta;thisisthoughttobebecausedesmoglein3isexpressedthroughouttheepidermisintheneonate;thisissimilartotheexpressionofdesmoglein3infull-thicknessoralepithelium,preventingoralinvolvementinPF

• Drug-induced:Thiol-drugs,sulfa-releasingdrugs• DDx:Impetigo,subcornealpustulardermatosisofSneddon andWilkinson(neutrophilsonly,noacantholyticcells)

• Treatments: Similartopemphigusvulgaris

Pemphigus Vegetans• Clinical:Twotypes:Neumanntype(startsandendslikePV)andHallopeautype(beginswithpustules);ineithertype,bullaeorpustulesquicklyturnintovegetatingmalodorousplaques

• Histology: Suprabasilaracantholysiscanbesubtle;thereismarkedhyperplasiaandpapillo-matosisoftheepidermiswithcharacteristiceosinophilicabscesses

• Acantholysisinsuprabasilarandsubcornealareas• Prominentpapillomatosissuggestsvegetatingnatureofthedisease

Pemphigus Vulgaris (PV)• Clinical:Flaccid,thin-walledbullae,easilyruptured,erosions,crusts,healwithhyperpigmentation,desquamativegingivitis,oralerosionsin60-100%,Nikolsky’ssignpositive,blistersspreadwithpressureonsurfaceofblister(Asboe-Hansensign)

• Histology: Suprabasilaracantholysiswith“tombstoning”ofbasallayer;acantholysis involveshairfollicles/adnexae;eosinophilsandneutrophilsintheinfiltrate

• Importantnote:acantholysiscaninvolvehairfolliclesandsebaceousglands• DIF: IntercellularIgG4>C3(maybemoreprominentinlowerepidermis)• IIF: (Monkeyesophagusbest)intercellularin80-90%;canfollowthesetiterstofollowdiseaseactivity

• Abs:Againstdesmoglein3(mucosal)anddesmoglein1and3(mucocutaneous)

PEARL

w I IF Substrates and Diseases RatBladder– ParaneoplasticPemphigus GuineaPigEsophagus–PemphigusFoliaceus

MonkeyEsophagus–PemphigusVulgaris


• ELISA:Testingagainstdsg1and/ordsg3canbeusedtofollowdiseaseactivity• Drug-induced: Pyrazolonederivatives,thiol-drugs,rifampin,penicillins,cephalosporins• Associations: Various HLA markers (DR4, DR14, B15, etc.)• Treatments:Steroids,azathioprine,mycophenolatemofetil,cyclophosphamide,IVIg

Porphyrias•Porphyria, Congenital

Erythropoietic Porphyria (Gunther’s)

• Clinical: Severephotosensitivitythatleads to mutilation iflightnotavoided,erythrodontia

• Treatment: Sunavoidance,bonemarrowtransplantPorphyria Cutanea Tarda• Clinical: Dorsalhands/scalp/facewithblistersthathealwithscarring/milia,hypertrichosis,hyperpigmentation,sclerodermoidchanges

• Histology:Minimalinflammatoryinfiltrate,fibrincuffing(PAS+)ofvesselsistypeIVcollagen,caterpillarbodiesinepidermis,festooningofpapillarydermisatbaseofblister

• DIF: LinearIgG,IgM,IgA,C3,fibrinogenatbasementmembraneandaroundvessels

• IIF: Negative

• Porphyrin profile: Urineuroporphyrin/coproporphyrin,stoolisocoproporphyrin

• Associations: Hemochromatosis(C282Ygene),hepatitisC,HIV,lupuserythematosus,hematologicmalignancies

• Treatment:Phlebotomy,antimalarialsPorphyria, Erythropoietic Protoporphyria Type

• Clinical: Painwithsunexposure,waxythickeningofknuckles/nose,gallstones,liverfailure

• Histology:Eosinophilicthickeneddepositsaroundbloodvesselsinupper/middermis

• Treatment:Betacarotene,N-acetylcysteinePorphyria, Variegate and Hereditary Coproporphyria• Clinical:SkinmanifestationslikePCTwithacuteabdominalattackslikeacuteintermittentporphyria

Pseudoporphyria (seeMnemonic)• Drug-induced: NSAIDS–mostcommonlynaprosyn,nabumetone,oxaprozin,alsoCelebrex;tanningbeds;hemodialysis;tetracycline;nalidixicacid;thiazides;furosemide;cyclosporine;etretinate;isotretinoin;amiodarone

• Urine,blood,fecalporphyrinsarenormal

PEARL

w Board Tips: Variegateporphyriahasacharacteristicemissionpeakat626nm;gallstonesassociatedwitherythropoieticprotoporphyria;noporphyrinsinurineinerythropoieticprotoporphyria;noskinchangesinacuteintermittentporphyria

PEARL

wDDx of Non-inflammatory Bullae: PCT,pseudoporphyria,non-inflammatoryEBA,bullousdiabeticorum,suctionorfrictionbullae,EB,patientondialysis

uTIPaDisease: Inheritance Enzyme Defect

Acuteintermittentporphyria–AD . . . . . . . . . . . Porphobilinogendeaminase

Congenitalerythropoieticporphyria–AR . . . . UroporphyrinogensynthetaseIII

Porphyriacutaneatarda–sporadicandAD . . . .Uroporphyrinogendecarboxylase

Hepato-erythropoieticporphyria–AR . . . . . . . Uroporphyrinogendecarboxylase

Hereditarycoproporphyria–AD . . . . . . . . . . . . . Coproporphyrinogenoxidase

Variegateporphyria–AD . . . . . . . . . . . . . . . . . . . Protoporphyrinogenoxidase

Erythropoieticprotoporphyria–ADandAR . . .Ferrochelatase

PEARL

w Distinguishvariegateandhereditarycopropor-phyriabyporphyrinprofile:thelattershouldhavemuchmorecoproporphyrininurineandstoolthantheformer

MNEMONIC Let’s Really Party Hard T(w)onight

Lasix Retinoids Pyridoxine Hemodialysis Thiazides TanningBeds NSAIDS


Staphylococcal Scalded Skin Syndrome(Ritter’sDisease)• Clinical: Patientspresentwithfever,skintendernessanderythemathatleadstoageneralizedsuperficialexfoliation;generallyadiseaseofinfantsoryoungchildrenbutoccasionallyadultswithdecreasedrenalfunction

• Histology:Separationissubcorneal

• InfectiousagentisStaphylococcigroup2phagetype71,whichproducesanexfoliativetoxinthatcleavesdesmoglein1

Stevens-Johnson Syndrome• Clinical:Patientsaresickwithfever,severemucosal/conjunctivalulcerationsandoccasionalGU/GIinvolvement

• Abs:AgainstdesmoplakinIandIIhavebeendescribed

Transient Bullous Dermolysis of the Newborn• MaybeavariantofdominantdystrophicEB• MutationshavebeenfoundintypeVIIcollagen• Blistersusuallydisappearbyage2

12.4 DISEASES THAT CAN PRESENT WITH BULLAE

Bullous Diabeticorum• Clinical:Tenseblistersonnon-inflamedbase,generallyonlegs/acral,oftenappearsuddenly• Histology:Intra-orsub-epidermalbullae,non-inflammatory• DIF: Generallynegative

Bullous Impetigo• Fragilebullaeresemblingpemphigus;easyruptureleadstoannularcrustedlesions• OftensecondarytoStaphylococcigroup2phagetype71

Bullous Insect Bite• Clinical:Maybemorecommoninpatientswithchroniclymphocyticleukemia• Histology:Typicalfindingsofaninsectbite(intraepidermalspongiosiswitheosinophilsanddermalinflammationwitheosinophils),butintraepidermalspongiosisismoresevereandconfluentcreatingbullae

Bullous Lichen Planus• Lichenplanuscansometimespresentwithbullae(ascananyinterfacedermatitis);truebullouslichenplanusisthoughttoarisesecondarytoextensiveinterfacechange(andthereforebullaeariseinexistinglesionsoflichenplanus)

• Somepatientshavefeaturesoflichenplanusaswellasbullouspemphigoid,andblistersariseonnormalskin(notinpre-existinglesionsoflichenplanus);somehavereferredtothisaslichenplanuspemphigoides;thesepatientsoftenhavecirculatingantibodiesagainstBPAg2

• DIFcanshowIgMandC3incolloidbodies

PEARL

w Drug-induced: Majorcauses=sulfonamides,anticonvulsants,NSAIDS,allopurinol


Bullous Lupus Erythematosus• Clinical: Non-inflamedbullae• Histology:Canlooklikedermatitisherpetiformis• DIF: LinearIgG,IgM,IgA,C3,fibrinogen• IIF: Generallynegative• Abs:AgainsttypeVIIcollagen

Bullous Mastocytosis• IgE-mediatedreleasers:PCN

Coma Blister• Clinical:Tenseblisteratpressuresites• Histology: Intra-orsub-epidermalblisterwitheccrineglandnecrosis• DIF: Generallynegative

Congenital Syphilis• Unlikeotherformsofsyphilis,congenitalsyphiliscanpresentwithbullae

Drug-Induced Bullae• Anydrugeruption(fixeddrug,erythemamultiforme,etc.)caneventuateinbullae

Friction Blister• Clinical:Bullaeoninflamedornon-inflamedbase,usuallysoles/hands• Histology: Generallyintraepidermal(usuallywithingranularlayer)

Sucking Blister• Clinical:Ablisterordenudedareaseeninneonates,secondarytosuckingtheareaoftheblisterinutero;generallyseenonthehand/wrist/forearm

12.5 VESICULAR DISORDERSAcropustulosis of Infancy

• Clinical: Recurrentextremelypruriticvesiculareruption(incrops)onpalms/solesofinfants/toddlers,needtoruleoutscabies;onsetusually3–6months,disappearsbyage3-4yearsold;verydifficulttotreat;dapsonemaybehelpful

• Histology:Subcornealvesiclecontainingneutrophils

Acute Eczematous Dermatitis• Intraepidermalvesiclesduetospongiosiswithexocytosisofneutrophilsandlymphocytes• DDx:Allergiccontactdermatitis(eosinophils),irritantcontactdermatitis(epidermalnecrosis,neutrophils,usuallyfewtonoeosinophils),acutenummulardermatitis(feweosinophils),idreaction,photodermatitis

Allergic Contact Dermatitis• AtypeIVhypersensitivityreaction(delayedhypersensitivity)(cell-mediated)• AhaptencombineswithaproteinwithinLangerhanscellstoproducethereaction• Patchtestingisthegoldstandardfordiagnosis• Irritantcontactdermatitisismorecommonthanallergiccontactdermatitis(~4:1)• RecentstudyintheJAADsuggeststhatoccupationaldermatitidesmayhaveanallergicetiologyinmorecasesthanpreviousstatisticsindicate

uTIPa�Direct Histamine Releasers: Opiates,succinylcholine,

d-tubocurarine,polymixinB,radiocontrast,vancomycin, thiamine


Atopic Dermatitis• Clinical:Ininfantspresentsonthecheeks/extensors(sparesdiaperarea);inchildhoodandadulthoodismorechronicwithlichenificationandincreasedinvolvementofflexuralareas

• Associatedwithafamilyorpersonalhistoryofatopy(asthma,hayfever,allergicrhinitis)• Increasedsusceptibilitytoviral(herpes,molluscum,papilloma),bacterial(especially

S. aureus),anddermatophyteinfections• Affects10-20%ofthepopulation;associatedwithfilaggrinmutations• Histology:Showsspongioticdermatitis,oftenwitheosinophils• Hertoghe’ssign:thinningoflateraleyebrows

• Th2typereaction(IL4,IL5,IL6,IL10,IL13)• Majorcriteria(ofHanifin):need31.) Pruritus2.)Typicalmorphologyanddistribution3.) Chronicity4.)Personalorfamilyhistoryofatopy

• Minorcriteria:need3/23(notalllisted): xerosis,hyperlinearpalms,increasedIgE,increasedS. aureus infections,hand/footdermatitis,nippledermatitis,cheilitis,conjunctivitis,Dennie-Morganfold,anteriorcataracts,facialpallor,pityriasisalba,intolerancetowool,perifollicularaccentuation

•Pathogenesisrelatedtofilaggrinmutations

Eczematous Dermatitis• Broadcategorythatincludesallergic/irritantdermatitis,atopicdermatitis,seborrheicdermatitis,etc.

• Dermatitisassociatedwithsystemicdisease:– Familial Leiner’s disease – fataldiseaseofinfantswithseborrhea,diarrheaanddeath

duetosepsis,associatedwithdecreasedC3/C5– Hyper IgE disease (Job’s) –AD–recurrentpyogenicinfectionsassociatedwithsevere

IgEelevationanddeficientchemotaxis– Wiskott-Aldrich–XLR–purpura,thrombocytopenia,severeinfections/lymphoma;

WASPgene– Chronic granulomatous disease – XLR–perioraldermatitis,cervicaladenitis,lungand

bonegranulomas/infections,deathinchildhood,secondarytodefectinneutrophils;CGDgene

– Langerhans cell histiocytosis –presentationmaymimicthatofaneczematousdermatitis,especiallyseborrheicdermatitis-like,ininfants,withinvolvementofscalpandintertriginousareas

Erythema Toxicum Neonatorum • Clinical: Papulesandpustulesthatstartwithin48hoursofbirthlasting2-3days;affectstheface/trunk/proximalextremities;sparesthepalms/soles;scrapingandGramstainrevealseosinophils;germtubeswouldbeseeninCandidalinfection;clinicallyoftenlookslikea“flea-bitten”rash

• Histology: Intraepidermalblister(inhairfollicle)containingeosinophils• Affectsupto40-50%ofinfants,causeunknown• Note:Baby’sskinhassmallhairfollicles,smalleccrineglands,increasednumberofnucleiinthecollagen


Grover’s Disease (TransientAcantholyticDyskeratosis)• Clinical: Pruriticfolliculitisoverthechest/abdomen/occasionallyback,generallyinmiddle-agedmen

• Histology:Canresemblepemphigusvulgaris,Darier’s,eczematousdermatitis,Hailey-Hailey

Incontinentia Pigmenti• Clinical:Presentswithdifferentstages:vesicles/bullae(1st2weeksoflife)thatbecomehyperkeratoticandverrucous(2-6weeksoflife),resolvingwithhyperpigmentationandsometimeshypopigmentation;mayhaveabnormalteethand/oralopecia

• Histology:Evidenceofspongiosiswitheosinophilsandapoptotickeratinocytes

• X-linkeddominant,genemutationinNEMO

Irritant Contact Dermatitis• Irritantsproduceareactioninalmostallpeopleexposedtotheirritantandisnotdependentonanimmunologic(memory)reaction

• Commonirritantsincludeacids(includingphenol,whichcanbeneutralizedbyisopropylalcohol),alkalis,detergents,fiberglass(removedwithtalcumpowder),hydrocarbons,mace,metalsalts,teargas(choloroacetophenone),water

• Chlorinatedcompoundsarealsoirritantsandcanalsoproducechloracne;examplesofchlorinatedcompoundsincludechloronaphthalene,chlorodiphenyl,dichlorobenzonitrile,tetrachloroazooxybenzene;dioxinintheVietnamwar;cuttingoils

• Chloracneischaracterizedbyfollicularpapules,especiallyintheretroauricular/malar/scrotalarea

Miliaria Crystallina • Clinical: Likedropsofwaterontheskin• Histology:Subcornealblister(fragile)formedneartheeccrineductcomingtothesurface• Theonlymiliariaofnewbornasittakesseveraldaystogetmiliariarubra• Isfrommechanicalobstruction;canseewithsunburnorfebrileillness

Miliaria Rubra (PricklyHeat)• Clinical:Lesionsaresmallpruriticpapuleswitherythema,seeninsweatingwithocclusivecoverings

• Histology:Sweatductobstructedindeeperepidermis,spongioticvesicleswithinflammatorycells

• Bacteriaareafactorinobstruction

Photodermatitis• Oftenonface/arms/Vofchest• Canresembleanairbornecontactdermatitis,butphotodermatitisgenerallysparestheuppereyelids,retroauricularandsubmentalareas

Pustular Psoriasis• Generalizedform(vonZumbusch):clinicallypatientsareusuallysickwithfever/chills;bodyiserythrodermicwithpustulesformingconfluent“lakesofpus”;oftenaprecedinghistoryofplaque-typepsoriasis

• Maybeinducedbywithdrawalofsteroids,iodides,terbinafine,minocycline,salicylates


Seborrheic Dermatitis• DevelopmentofseborrheicdermatitisisrelatedtoMalassezia furfur andsebumproduction• Seenininfantsandpost-pubertally;greasy,well-demarcatedpinktosalmon-coloredthinplaquesontheface/scalp/chest/back/intertriginousareas

Stasis Dermatitis• Subacutetochronicdermatitiswithhemosiderin,dilatedcapillariesinfibroticdermis• Maybeexacerbatedbyapplicationoftopicalsteroidsortopicalantibioticsifaconcomitantallergiccontactdermatitisispresent

Subcorneal Pustulosis of Sneddon and Wilkinson• Histology:Subcornealpustuleswithmanyneutrophils,no“clingons”• DDx:Pustularpsoriasis,impetigo,pemphigusfoliaceus,acropustulosisofinfancy,IgApemphigus

Transient Neonatal Pustular Melanosis• Clinical:Affects4%ofblacks,<1%ofwhites;flaccidvesiculopustules(non-inflamedbase)developover1-2dayswhichruptureandleaveacollaretteofscale,resolvingwithhyperpigmentedmaculesthatlast1-2weeks

• Sitescommonlyaffectedaretheforehead,neck• Histology: Subcornealpustules(sterile);hyperpigmentedmaculesshowincreasedbasilarpigmentation

12.6 COMMON ALLERGENSFragrance Mix

• Containscinnamicalcoholandaldehyde,hydroxycitronellal,isoeugenol,eugenol,oakmossabsolute,alpha-amylcinnamicaldehyde,geraniol

• Foundinperfumes,cinnamonoil/powder,cassiaoil,flavoringagents,toiletsoaps,bathtissue• BalsamofPeru,anotherallergen,isalsoafragrance;fromtheMyroxylon pereiraetree;isfoundnaturallyintomatoes/citrus;incola

Gold• Patientsallergictogoldoftenalsoreacttonickelandcobalt

Cobalt• Patientsoftenalsoreacttogold/nickel• Foundinjewelry,cosmetics,cements

Imidazolidinyl Urea = Germall 115 = Tristat• Apreservative,aformaldehyde-releaser• Foundincosmetics/creams/lotions/hairconditioner/shampoo/deodorants,OTCmeds,adhesives,bubblebaths,cleaningagents,latexemulsions,inks,soaps

•Cross-reactswithformaldehydeanddiazolidinylurea

Lanolin• Foundinwoolalcohol,woolwax,woolfat,adhesives,cosmetics,topicalmedications(creams/lotions/ointments),soaps


• Fromsheepfleece• Lanolin-sensitivepatientscansometimestolerateoneformulationbutnotanother• Commonallergyamonglegulcerpatients

Methylchloroisothiazinolone = Kathon CG = 5-chloro-2-methyl-4-isothiazolin-3-one• Foundincosmetics,skin/hairproducts,“acid”permanentwaves,industrialwatersystems,coolingoils,soaps,latexemulsions,moisttoiletpaper,mascara,biocides

• Apreservative• Maycauseairbornecontactdermatitis

Neomycin• Mostcommonsensitizingtopicalantibiotic• Foundintopicalantibiotics,first-aidcreams,eardrops,nosedrops• Cross-reactivitywithotheraminoglycosides;allergytobacitracinoftencoexists

Nickel• Mostcommonallergen• Foundinjewelry,alloys,pigments,dentures,orthopedicappliances,scissors,razors,eyeglassframes,eatingutensils

• Cantestforthepresenceofnickelbyusingdimethylglyoxime

Para-Phenylenediamine• Foundinhairdyes,inks,photodevelopingsolutions,textiledyes

• Foundinhennatattoos

Para-Tert-Butylphenol Formaldehyde Resin• Foundinshoes,watchstraps,do-it-yourselfglues,plywood,insulation,automobiles,motoroils,inks,papers,filmdevelopers,disinfectants,deodorants,dentalbonding,rubber,raincoat

• Maycausedepigmentation

Quaternium-15 = Dowicil 200 • Apreservative,aformaldehyde-releaser• Foundincosmetics,householdcleaners/polishes,creams/lotions,shampoo,latexpaints,topicalmeds,metalworkingfluids,adhesives

• Notallpatientsallergictothisareallergictoformaldehyde

Rosin (Colophony)• Foundinadhesivetape,cosmetics,insulatingtape,glossypaper,flypaper,polish,paints,inks,epilationwax,rosinbagsforbaseballplayers,varnishes,violinbows,chewinggum

• From Pinus palustris and Pinus caribaea (conifers)

• A.k.a.abieticacid

Thimerosal(Merthiolate)• Preservativeinvaccines(e.g.,hepatitis),eyedropsolutions,cosmetics,nasalsprays• Cross-reactivitywithmercuryorduetothethiosalicylicacidcomponent• Cross-reactswithpiroxicam

PEARL

w Cross-reactivitywithazo-andanilinedyes,procaine,benzocaine,PABA,para-aminosalicylicacid,sulfonamides


Chromate

• Foundinleather,cements,somegreenfelts(pooltables)

Thiuram Mix• Inrubber(preventsdegradation),latex,adhesives,pesticides,medicationslikeAntabuse• Foundincondoms,adhesives,diaphragms,repellents,fungicides• Includesfourchemicals

12.7 PLANT ALLERGENS (Oftencauseacutevesiculationanderythemainlineararrays)

Family Alliaceae• Includesgarlic,onions,chives• Mostimportantallergeningarlicisdiallyldisulfide• Garlicisalsoanirritant

Family Alstroemeriaceae and Family Liliaceae• Peruvianlily(alstroemeria)andtulips• Fingerdermatitisinflorists/gardernershandlingtulipbulbs• AllegenistulipalinA(ametabolizedproductoftuliposideA)• TulipalinA=alpha-methylene-gamma-butyrolactone

Family Anacardiaceae (ToxicodendronGenus)• InitiallyToxicodendronplantswereclassifiedasRhus

• Allergenisurushiol,apentadecacatechol• Causesblackdotdermatitis• Plantshavecharacteristicleavesarrangedinthrees

Family Apiaceae (FormerlyUmbelliferae), Moraceae, Rutaceae• Apiaceaeincludescelery,fennel,hogweed,parsnip• Moraceaeincludesthefigtree• Rutaceaeincludescitrus(lime,bergamotorange,lemon,rue)• Thesefamiliescancausephototoxicityduetofurocoumarins(psoralensandangelicins)

Family Asteraceae (FormerlyCompositae)• Clinicallyseechroniclichenificationofface/neck/hands/arms(light-exacerbated);areasofinvolvementcommonlyincludetheuppereyelids,retroauriculararea,andsubmentalarea(airborne)

• Fromartichokes,broomweed,chamomile,chrysanthemum,liverwort,ragweed,sagebrush,chicory,endives,tarragon,sunflower,marigold,dandelion

• Allergenissesquiterpenelactone• Permethrin(Elimite)isderivedfromchrysanthemums

Family Lamiaceae• Includeslavender,thyme,spearmint(allergen=carvone),peppermint(allergen=menthol)

PEARL

wUrushiolisfoundinmangopeel,poisonivy(toxi-codendrontoxicarum),poisonoak(toxicodendrondiversilobuminwesternU.S.),sumac,gingkofruit(allergenisacross-reactor–ginkgolicacid),lac-quertree,cashewnut,Indianmarkingnut,blackvarnishtree,Brazilianpeppertree


Family Primulaceae• Primulaobconica(primrose)• Allergenisprimin(2-methoxy-6-pentyl-benzoquinone),aquinone

Family Urticaceae• Includesnettles(Urtica dioica)• Theseplantscontainhistamine,acetylcholine,andserotoninamongotherproducts,allowingthemtocauseurticariauponcontact

12.8 TIPS• Cotton,silk,nylon,linenrarelysensitize;100%polyestermaybebestforformaldehyde-sensitivepatients

• Spandexcontainsmercaptobenzathiazole• Glycerylthioglycolateisinacidpermanentwaves

• Tosylamideformaldehyderesinandethylacrylatecancausedermatitisnearnails

• TRUEtestdoesnottestforgoldallergyandonlytestsforformaldehydeandquaternium-15(butnototherformaldehydereleasers)allergy

• Melaleucaplant(teatreeoil)–allergenisd-limonene

• Castorbean–allergenisricin

PEARLw Common Allergens by Site eyelids rubber,nailproducts(ethylmethacrylate,methylmethacrylate,tosylamideformalde-

hyde,resin,glutaraldehyde,benzalkoniumchloride),eyeproducts

forehead hatband(rubber),leather

scalp/retroauricular hairdye/products,permanentwave

perioral gum,foods

neck fragrance

earlobe nickel

abdomen nickel

trunk formaldehyde

axillaryvault deodorant

axillaryfolds clothingdyes,formaldehyde

backofwomen brastrap(rubber),nickel

wrist chromates(leather)

hands gloves(latex,rubberespeciallythiurams),ethylmethacrylateindentists/surgeons

waist rubber

perianal suppositories(“caine”anesthetics)

shins socks(rubber)

feet(sparestoewebs) shoes(rubberespeciallymercaptobenzothiazole,chromatesinleather)

ulcers bacitracin,neomycin,lanolin

penis poisonivy,rubber/latex(condoms)

uTIPa�TixocortolpivalatetestsforClassAcorticosteroid

allergy(predictsallergytohydrocortisone,prednisone)

a�BudesonidetestsforClassBandDcorticosteroidallergy(predictsallergytotriamcinoloneand hydrocortisonebutyrate)

uTIPa Corticosteroid Classes

ClassA:Hydrocortisone,methylprednisdone, prednisone,prednisolone

ClassB:amcinonide,budesonide,desonide, flucinonide,fluocinoloneacetonide,halcinonide, triamcinolone

ClassC:betamethasone,dexamethasone,flucortisone

ClassD:aclomethasone,betamethasonevalerate


• Lichens–allergenisusnicacid,evenicacid,atronorin• Latexallergy–cancross-reactwithavocado,banana,chestnut,kiwi• Hydroquinonecanbefoundinrubberproducts• Cocamidopropylbetaine–putativeallergenisamidoamine;foundinshampoos,cosmetics,

and conditioners• Glutaraldehydeandbenzalkoniumchloride(foundinbabywipes)arebothcoldsterilizers• Dispersebluedyesareamajorcauseoftextileallergy• Ethylenediamine–apreservative;cross-reactswithhydroxyzine

12.9 PLANT IRRITANTSFamily Alliaceae

• Includesgarlic,radish(thiocyanatesinthebulbsareirritating)

Family Amaryllidaceae• Includesdaffodil,narcissus,hyacinth• Bulbscontaincalciumoxalate

Family Araceae• Includesthedumbcaneplant(Dieffenbachia),averycommonhouseplant• Irritantiscalciumoxalate

Family Euphorbiaceae• Includesthecrotonplant,spurges• Phorbolestersaretheirritant

Family Ranunculaceae• Includesbuttercupsandmarigolds• Theirritantisprotoanemonin

Family Solanaceae• Includescapsaicin(neutralizedwithvinegar)

ACKNOWLEDGMENTS

GaryCole,MD EdwardJeffes,MD,PhD

BruceE.Strober,MD,PhD

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allyseparableepitopesontheBP180ectodomain:EvidencethatBP180spansthelaminalucida.J Invest Dermatol1997;108:901-907.

4. SardyM,etal.Epidermaltransglutaminase(TGase3)istheautoantigenofdermatitisherpetiformis.J Exp Med2002;195:747-757.

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7. CunninghamMJ,ZoneJJ.Thyroidabnormalitiesindermatitisherpetiformis.Ann Intern Med 1985;102: 194-196.8. CollinP,ReunalaT.Recognitionandmanagementofthecutaneousmanifestationsofceliacdisease:aguide

fordermatologists.Am J Clin Dermatol 2003;4:13-20.9. BrennerS,Bialy-GolanA,RuoccoV.Drug-inducedpemphigus.Clin Dermatol 1998;16:393-397.10. UittoJ,PulkkinenL.Moleculargeneticsofheritableblisteringdisorders.Arch Dermatol2001;137:1458-1461.11. ChenM,etal.Theepidermolysisbullosaacquisitaantigen(typeVIIcollagen)ispresentinhumancolonand

patientswithcrohn’sdiseasehaveautoantibodiestotypeVIIcollagen.J Invest Dermatol 2002;118:1059-1064.12. ChanLS,ChenM,WoodleyDT.Epidermolysisbullosaacquisitaintheelderly.J Geriatr Dermatol 1996;4: 47-52.13. ShornickJK,BlackMM.Secondaryautoimmunediseasesinherpesgestationis(pemphigoidgestationis).J

Am Acad Dermatol 1992;26:563-566.14. DjahansouziS,etal.Herpesgestationismaypresentitselfasaparaneoplasticsyndromeofchoriocarcino-

ma—acasereport.Gynecol Oncol2003;89:334-337.15. HerronMD,ZoneJJ.DermatitisherpetiformisandlinearIgAbullousdermatosis.InBologniaJL,JorizzoJL,

RapiniRP,Eds.Dermatology.London:Mosby,2003;479-489.16. AmagaiM.Pemphigus.InBologniaJL,JorizzoJL,RapiniRP,Eds.Dermatology.Mosby,London,2003;449-462.17. FoedingerD,etal.AutoantibodeistodesmoplakinIandIIinpatientswitherythemamultiforme.J Exp Med

1995;181:169-179.18. KucenicMJ,BelsitoDV.Occupationalallergiccontactdermatitisismoreprevalentthanirritantcontactder-

matitis:A5-yearstudy.J Am Acad Dermatol2002;46:695-699.


NOTES


NOTES

Technology

ETAS_12 bullous