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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
Bullous and Vesicular Dermatoses 417
For practice exam questions and interactive study tools, visit the Dermatology In-Review Online
Practice Exam and Study System at
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Bullous and Vesicular Dermatoses 419
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
Bullous and Vesicular Dermatoses 421
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
422 2011/2012DermatologyIn-Review l Committed to Your Future
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
Bullous and Vesicular Dermatoses 423
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
424 2011/2012DermatologyIn-Review l Committed to Your Future
• 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
Bullous and Vesicular Dermatoses 425
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
426 2011/2012DermatologyIn-Review l Committed to Your Future
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%)
Bullous and Vesicular Dermatoses 427
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
428 2011/2012DermatologyIn-Review l Committed to Your Future
• 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
Bullous and Vesicular Dermatoses 429
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
430 2011/2012DermatologyIn-Review l Committed to Your Future
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
Bullous and Vesicular Dermatoses 431
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
432 2011/2012DermatologyIn-Review l Committed to Your Future
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
Bullous and Vesicular Dermatoses 433
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
434 2011/2012DermatologyIn-Review l Committed to Your Future
• 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
Bullous and Vesicular Dermatoses 435
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
436 2011/2012DermatologyIn-Review l Committed to Your Future
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
Bullous and Vesicular Dermatoses 437
• 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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