vesiculobullous lesions, pempigus ppt

oral vesiculo bullous lesions pemphigus

1. •FITZPATRICKCLASSIFICATION -ACCORDING TO
ANATOMICAL PLANE
A.INTRAEPIDERMALBLSTER
I.GRANULAR LAYER
a)PEMPHIGUSFOLIACEOUS
b)PEMPHIGUSERYTHEMATOSUS
c)FRICTIONALBLISTERS
d)STAPHYLOCOCCAL SCALDEDSYNDROME
Vesiculo-bullous Diseases

2. II.SPINOUSLAYER
a)ECZEMATOUS DERMATITIS
b)SECONDARY TOHEATORCOLD
c)HERPESVIRUSINFECTION
d)FAMILIALBENIGNPEMPHIGUS
III.SUPRABASAL
a)PEMPHIGUSVULGARIS
b)PEMPHIGUSVEGETANS
c)DARIER’SDISEASE
IV.BASALLAYER
a)ERYTHEMAMULTIFORMAE
b)TOXICEPIDERMALNECROLYSIS
c)LUPUSERYTHEMATOSUS
d)LICHENPLANUS
e)EPIDERMOLYSISBULLOSASIMPLEX

3. B.DERMAL-EPIDERMALJUNCTIONALZONE
I.LAMINALUCIDA
a)BULLOUSPEMPHIGOID
b)CICATRICIALPEMPHIGOID
c)EPIDERMOLYSIS BULLOSA–JUNCTIONAL
II.BELOWBASALLAMINA
a)ERYTHEMA MULTIFORMAE
b)EPIDERMOLYSIS BULLOSA–DYSTROPHICA

4. 1.PRIMARYBLISTERING
a)PEMPHIGUS
b)BULLOUSPEMPHIGOID
c)CICATRICIALPEMPHIGOID
d)EPIDERMOLYSIS BULLOSAACQUTISA
2.SECONDARY BLISTERING
a)CONTACTDERMATITIS/STOMATITIS
b)ERYTHEMA MULTIFORMAE
c)TOXICEPIDERMALNECROLYSIS
2
nd
Classification

5. 3. INFECTION
a) VARICELLA ZOSTER
b) HERPES SIMPLEX
c) BULLOUS IMPETIGO
4. SYSTEMIC DISEASE
a) INFECTION –CUTANEOUS EMBOLI
5. METABOLIC
a) DIABETIC WITH BULLAE
b) PORPHYRIA CUTANEA TARDA

6. Pemphigus

7. •Pemphix=Bubble/Blister
•Pemphigusisaserious,autoimmunechronicskindisease
characterizedbyappearanceofvesiclesandbullae,smallto
largefluidfilledblistersonskinaswellasmucousmembrane
thatdevelopincycles.
•Characterizedbythefindingofcirculatingimmunoglobulin
G(IgG)antibodydirectedagainstthecellsurfaceof
keratinocytes
•DerievedfromGreekword
•Whichmanin1971.
•Itaffects0.1to0.5patientsper100000populationperyear

8. •Fourprimarysubsets:
–PemphigusVulgaris
–PemphigusVegetans
–PemphigusFoliaceous
–Paraneoplasticpemphigus
•70%ofpemphiguscasesarePemphigusvulgaris

9. •Pathogenesis:
–Itisanautoimmunediseasewhereautoantibodiesattack
thekertinocytecelljunctionsleadingtodestructionof
tonofilamentcomplex,resultinginthelossofattachment
fromcelltocell
–Theseantibodiesarereactiveagainstthedesmosomesor
thetonofilamentcomplex,specificallytoDesmoglein-1
andDesmoglein-3
–TheCirculatingantibodiesareoftypeIgG1&IgG4
subclasses
Pemphigus Vulgaris

12. •Ageofonsetapprox.50-60yrs
•Numerousrapidlyappearingvesiclesandbullaeofvarying
diameter
•Containthin,wateryfluidinbeginningwhichlaterbecomes
purulentorsanguineous
•Rupturedvesiclesandbullaeleaverawerodedsurface
General Clinical Features

14. •Nikolsky’ssign:dislodgementofintactsuperficialepidermis
byashearingforce,indicatingaplaneofcleavageinthe
skin.Rubbingofapparentlyunaffectedskinleadingtoloss
ofsuperficialepithelium.
•Characteristicsignofpemphigusandiscausedby
perivesicularedemawhichdisruptsthedermal-epidermal
junction

16. •Mucosallesionsmayprecedeskinmanifestationsbymonths
•50-70%ofptswithP.Vulgarisshowmucosalinvolvement
•Intactvesicles&bullaearerareandmostoftenptspresent
withill-defined,irregularlyshaped,gingival,buccalor
palatineerosionswhicharepainfulandslowtoheal
•Erosionscanspreadtoinvolvelarynxwithsubsequent
hoarsenessofvoice.
•Othermucosalsurfacesmaybeinvolvedsuchasconjunctiva,
genitalregions,etc.
Oral Manifestations

20. •Intraepithelialblisterformationjustabovethebasallayer
producing“SuprabasilarSplit”
•Prevesicularedemaweakensthejunctionsandintercellular
bridgesbetweenepithelialcellsdisappear,resultinginlossof
cohesivenessorAcantholysis
•Fluidfilledvesicularspaceisformedbetweenthebasaland
parabasallayersofepithelium.
•Basalcellsareintactandshowa“tomb-stone”appearance
Histologic Features

22. •Tzanckcells:Clumpsofepithelialcellsfoundwithinthe
vesicularspaceoffreshlyopenedvesiclesorbulla
•Characterizedbydegenerativechangesincludingswellingof
nuclei,hyperchromaticstainingandmarkedincreasein
RNAcontentofthecytoplasm.
•SuchSmearsfromptswithpemphiguscomfirmingthe
typicaltzanckcellsiscalledas“TzanckTest”

24. •1-2dayoldvesiclesandbullaecontainvariablenumbersof
Neutrophilsandlymphocytes
•Relativescarcityofinflammatorycellinfiltrationinvesicle
andattheconnectivetissuebaseisconfirmatoryof
Pemphigus

25. •Directimmunofluorescencedemonstratesimmunoglobulins,
especiallyIgGaloneorincombinationwithC3,IgAorIgM,
intheintercellularspacesofclinicallynormaladjacent
epithelium
•GRANULAR orFISH-NET patternseenin
immunoflourescence
•Indirectimmunofluorescencecanalsobeusedindiagnosis
Immunoflourescence studies

28. •RarevariantandOccursin1-2%ofpemphigusvulgaris
•2clinicalvariantsexistaccordingtoinitialpresentation:
–NeumannType:Flaccidbullae&Erosionsseen
–Hallopeau:Pustulesseen
•Bothsubtypeseventuallydevelophyperpigmented
vegetativeplaqueswithpustulesandhypertrophic
granulationtissueatperiphery
Pemphigus Vegetans

29. •ClinicallesionstypicallylocatedatIntertrigenousareas
andOralmucosa
•Cerebriformtongueisacharacteristicfeatureseenon
tongueofPemphigusvegetanscharacterizedbyapattern
ofGyri&Sulciondorsumoftongue
•Thesurfacesofthevermillionborderofthelips,thegums,
andthehardpalateshowmultiplewhiteverrucous
papules,fissures,erosions,andcrustsforminga
cobblestonepattern.

31. •IgG4subclassautoantibodiesdirectedtoDesmoglein-1
expressedmainlyingranularcelllayerofepidermis
•Precipitatingfactors:MedicationsorUltravioletRays
•6subtypesexist:
–Pemphiguserythematosus
–Pemphigusherpetiformis
–EndemicPemphigusfoliaceus
–ImmunoglobulinAPemhigus
–ParaneoplasticPemphigusfoliaceus
–Drug-inducedPemphigusfoliaceus
•MildtypeofpemphigusandOrallesionsarerare
Pemphigus Foliaceus

32. •Clinicalfeatures:Bullouslesionswhichrapidlyrupture
anddrytoleavemassesofflakesorscalessuggestiveof
exfoliativedermatitis
•Brazilianpemphigus(Fogoselvagem/Brazilianwildfire)
isamildendemicformseenofteninchildrenofbrazil
•Histopathology similar to pemphigus vulgaris with the
Acantholysis seen in the superficial epidermis

35. •Orallesionsandbullouseruptionssimilartopemphigus
developinginpatientswithunderlyingneoplasms
•Tumorantigensevokeanimmuneresponsethatleadsto
thedevelopmentofanautoimmuneresponseto
intercellularadhesins(plakins)
•Paraneoplasticpemphigusismostlyfatal
•OralManifestations:PainfulOralerosions&ulcerations
accompaniedwithcutaneouseruptionswhichcouldbe
morbilliform/urticarial/bullous/papulosquamous/or
erythemamultiformelikelesions
•Lips,gingiva,buccalmucosa,lingualmucosa,etccanbe
affected.Liplesionsshowerosions&crustingsimilarto
Stevenjohnsonsyndrome
Paraneoplastic Pemphigus

36. •Hailey–Haileydisease
•Autosomaldominantdiseaseshowinggeneticdefectof
“Calciumpumpprotein”
•Orallesionsoccuroccasionallyandthelesionsdevelop
cropsorvesicleswhichrapidlyruptureleavingraw
erodedareas
•Histopathology:Moreextensiveacantholysisthanin
pemphigusvulgarisandwithlessdamagetothe
acantholyticcells
•Occasionalpersistenceofintercellularbridgesbetween
acantholyticcellsandadjacentnormalcellsgivesa
DILAPIDATEDBRICKWALLeffect
Familial Benign Pemphigus

38. •Benignmucousmembranepemphigoid/Ocularpemphigus
•Autoantibodiestargetedagainstbasementmembranezone
antigens.SpecificallyIgG4antibodiesdirectedto:
–Bullouspemphigoidantigen-2(BPAG2)(BP180)
–Epiligrin(Laminin-5)
•Female:Male=2:1
•Usuallybetween40–50yrsofage
•Typicallythevesiculobullouslesionsoccuronoralmucosa
andconjunctivaaswellasskinlesionsaroundgenitaliaand
nearbodyorifices
•TheocularlesionstypicallyhealwithaSCARformation
Cicatricial Pemphigoid

41. •VesiculobullouslesionsprominentlyseenontheGingiva
whicharethick-walledandmaypersistfor24-48hrsbefore
rupturinganddesquamating
•Rupturedareaisraw,erodedandshowsbleedingsurface
•Gingivaemanifestpersistenterythemaforweekstomonths
afterhealing
•Orallesionsrarelyscar
Oral Manifestations

44. •Vesiclesandbullaearesub-epidermalratherthansupra-
basilarandthereisnoevidenceofacantholysis
•Basementmembranestructuresdetachalongwiththe
epitheliumfromtheunderlyingconnectivetissue
•Nonspecificchronicinflammatoryinfiltrateinthestroma
chieflylymphocytes,plasmacellsandeosinophils
•Immunofluorescencerevealscontinuouslinearbandof
fluorescenceatthebasementmembraneregion
Histological Features

47. Bullous Pemphigoid
Parapemphigus

48. •Parapemphigus
•Rarelyinvolvesmucousmembrane
•Autoantibodiesagainstbasementmembranezoneantigens:
–Bullouspemphigoidantigen-1(BPAG2)(BP230)
–Bullouspemphigoidantigen-2(BPAG2)(BP180)
•IgGantibodiesbindtobasementmembraneandactivate
complimentandinflammatorymediators.Theactivated
complimentattractsinflammatorycellstothebasement
membrane
Bullous Pemphigoid

49. •Diseaseofelderlypeople
•Generalizednon-specificrashuponthelimbswhichlater
showstheappearanceofvesiculobullouslesions
•Vesiclesandbullaearerelativelythickwalledandmay
remainintactforsomedays
•Lateritmayruptureandleavearawerodedareawhich
healsrapidly
•Orallesionsarerareandifpresenttheyaretypically
similartothoseofcicatricialpemphigoidandmostlyseen
onthegingiva(desquamativegingivitis)

52. •Bullaearesub-epidermalandnon-specificwithNo
evidenceofacantholysisandepitheliumappearsnormal
•Basementmembranestructuresremainattachedtothe
connectivetissueandseparatefromtheoverlying
epithelium
•Vesiclescontainfibrinousexudateadmixedwithoccasional
inflammatorycells
Histological Features