Chronic Vesikobulosa DermatosisChronic Vesikobulosa Dermatosis

• 1. Pemphigus

• 2. Bullous Pemphigoid

• 3. Dermatitis Herpetiformis

• 4. Chronic Bullous Disease of Childhood• 4. Chronic Bullous Disease of Childhood

• 5. Cicatrical Pemphigoid

• 6. Gestationes Pemphigoid

• 7. Bullous Epidermolysis

PemphigusPemphigus• Pemphigus: a group of

Autoimmune blistering

diseases of the skin &

mucous membranes�

characterized intra characterized intra

epidermal blisters due

to acantholysis

(separation of

epidermal cells from

each other)

Classification of PemphigusClassification of Pemphigus

Type Form

1. Pemphigus vulgaris P. Vegetans:

Localized

Drug-induce

2. Pemphigus foliaceus P. Erythematosus: localized

Fogo selvagem: Endemic drug

induce

3. Paraneoplastic pemphigus

IgA pemphigus Sub-corneal pustular dermatosis

Intraepidermal neutrophilic IgA

dermatosis

ImmunopathologicallyImmunopathologically

Bound and circulating IgG directed against the

cell surface of keratinocyte

P. Vulgaris (PV): blister in the deeper part of P. Vulgaris (PV): blister in the deeper part of

epidermis� above the basal

layer

P. Foliaceus (PF)= superficial pemphigus

� blister in the granular layer

ImmunofluorescenseImmunofluorescense

• The hallmark: IgG autoantibodies against the cell surface of keratinocyte (in pat’s serum� indirect IF

• Direct IF in PV & PF: IgG on the cell • Direct IF in PV & PF: IgG on the cell surface of KC in perilesional skin

• 80%> : pat. PV� circulating antiepithelial

cell surface IgG

Pemphigus antigenPemphigus antigen

- Desmogleins 3

- Transmembrane glycoproteins of desmosomes

(cell to cell adhesion structure)

� anti desmoglein 3 antibodies

anti desmoglein 1 antibodies

PV � affect predominnantly m. membrane :

only anti desmoglein 3 antibodies

PV mucocutaneus: anti desmg. 1 & 3 antibodies

Clinical ManifestationClinical Manifestation

Skin:

• Rarely pruritic� often painful

• Flaccid blister� arises on normal

appearing skin/ erythematous skin� fragile�

broken blister�erosions� often painfulbroken blister�erosions� often painful

erosions quite large� tendency to spread at

their periphery

Bulla> vesicles

Clinical ManifestationClinical Manifestation

• Nikolsky sign (+): active blister� applying lateral pressure to normal appearing skin

• Erosion� excessive granulation tissue &

crusting� intertrigenous areascrusting� intertrigenous areas

scalp, face

Mucous membrane: painful m. membrane

erosion ( 5 month

before skin lesion

develop)

Nikolsky sign (+)Nikolsky sign (+)

• Pemphigus

• Epidermolysis Bullosa

• Erythema Multiforme

• Toxic Epidermal Necrolysis• Toxic Epidermal Necrolysis

Clinical ManifestationClinical Manifestation• 52 % painful oral lesion� generalized in 5

months -1 year

• Some had oral lesions for > 5 years before generalization

• Intact blister are rare� because fragile &

break easily

Scattered� often extensive erosions (oral

cavity, buccal mocosa� pharynx, other

area)

Histopathology PVHistopathology PV

• Suprabasilar blister with acantholysis�

just above basal cell layer epidermal cells lose their normal cell to cell contact� form blister� KC in the blister cavityblister� KC in the blister cavity

basal layer stay attached to the BMZ�may lose the contact with their neigbors� row of tombstones

Bulla : intra epidermal/ supra basal

Tzanck TestTzanck Test

• To show acantholytic Epidermal cells

ImmunofluorescenceImmunofluorescence

• The hallmark: IgG autoantibodies against the cell surface of keratinocytes

• Indirect immnunofluorescence:• Indirect immnunofluorescence:

80 % pats. � have circulating

antiepithelial surface IgG

TreatmentTreatment

• Prednisone: high dose� disease activity is controlled� tapering pred.� low dose

• If combination immunosuppressive� dose intermediate/ low doseintermediate/ low dose

• Immunosuppressive:

mycophenolate mofetil (cellcept)

azathioprine (imuran)

cyclophoaphamide (cytoxan)

Bullous PemphigoidBullous Pemphigoid

• Usually occurs in elderly pat.

• Mortality 6%-40% in 1 year

• Pruritic urticarial lesions

• Tense large blisters• Tense large blisters

• Oral m. membrane erosions in minority of

pats

Direct Immunfluorescence C3 , IgG at epidermal basement membrane

Bullous pemphigoidBullous pemphigoid

ImmunofluorescenceImmunofluorescence

• Direct: C3 and IgG at epidermal basement membrane

• Indirect: antibasement membrane IgG in • Indirect: antibasement membrane IgG in serum

• Perilesional skin reveals immunoreactants deposited in linear pattern at epid basement membrane

AutoantigensAutoantigens

• Proteins in the Kc hemidesmosome a basal cell-basement membrane adhesion structurestructure

Etiology & pathogenesisEtiology & pathogenesis

• Electron microscopy: early blister formation occurs in the lamina lucida, between the basal cell membrane and the lamina densalamina densa

• Blister formation: there is loss anchoring filaments and hemidesmosome

degranulation of infiltrating leucocytes

ImmunofluorescenceImmunofluorescence

• Indirect IMF antibodies does not usually correlate with disease extent/ activity in contrast in pemphigus)

• C3 and other components classicals and • C3 and other components classicals and alternative complement pathways & complement regulatory protein B 1H� at BMZ

• Activated complement in blister fluid

Pemphigoid antigensPemphigoid antigens

• Immnunoelectron microscope: Ag in the hemidesmosome, an adhesion junction importants in anchoring the basal cell to BMZ

Clinical FindingsClinical Findings

• Bullous: large, tense, arising in normal

skin/ erythematous base

filled : clear fluid/ hemorrhagic

Eroded skin� tendency to reepithelize

The erosion do not tend to expand at the The erosion do not tend to expand at the

periphery

• Localisation: lower abdomen

inner / anterior thights

flexor forarms/ any where

The lesion� do not scar

Clinical FindingClinical Finding

• Usually : pruritus

• Sometimes: erythematous component�pat. with urticarial lesion

• Resolution : from the center, • Resolution : from the center, hyperpigmentation

• M. Membrane : 10-35%� limited oral MM

(buccal mocosa)

TreatmentTreatment

Localized BP: topical steroids

topical tacrolimus

Extensive disease� oral prednisone:

1mg/kg BB/day 1mg/kg BB/day

once a day

�Topical thy 40 gr/day clobetasol propionate cream 0,05%� 2 x/day

Immonosupresive: azathioprine

2525

Dermatitis HerpetiformisDermatitis Herpetiformis

• Characterized by an intensely itchy

• Chronic papulovesicular eruption

• Distribution symetrically on extensor surfaces

• Clearly distinguished from other subepidermal • Clearly distinguished from other subepidermal

blistering erup. By histologic, immunologic,

Gastro Intest Criteria

• Any age

• Associated gluten sensitive enteropathy

Etiology and pathogenesisEtiology and pathogenesis

• Antibodies to tissue transglutaminases (Tigases) in sera from DH.

• Epidermal tigase is the dominant autoantigen in DHautoantigen in DH

• Gluten a protein found in wheat, barley, rye

-> play a critical role in pathogenesis in DH

Gastro abnormality in pat. DH (60-75%)

DiagnosticDiagnostic

• Granular immunoglobulin A deposits in nomal appearing skin

• Assocated gluten sensitive enteropathy• Assocated gluten sensitive enteropathy

Clinical ManifestationClinical Manifestation

• Primary lesion: erythematous papule

urticarial like plaque/

vesicles >>

Large bullae occure infrequentlyLarge bullae occure infrequently

Vesicles in palm: hemorrhagic

Disappearance : hyperpigmentation &

hypopigmentation

Herpetiform (herpes like): group of lesions

Clinical ManifestationClinical Manifestation

• Symptoms: severe stinging, burning,

itching

Symetric distribution:

elbows, knees, buttock, shoulders and elbows, knees, buttock, shoulders and sacral areas

Most pat: scalp lesions and/or nuchal posterior, face and facial hairline

M. Memb. : uncommon as in palms & sole

Laboratory TestLaboratory Test

• Perilesional and uninvolved skin pat DH: granular (or fibrillar) Ig deposits located in dermal papilary tips� igA

• IgA deposits are unaffected by treatment • IgA deposits are unaffected by treatment with drugs� may decrease in intensity or disappear after long term adherence to gluten free diet

Laboratory FindingLaboratory Finding

• IgA1 (produce in bone marrow) >

• IgA2 (produced in gut secretion)

• Complement (C3)� the same location as IgA

• C3� is not affected by treatment with dapson, • C3� is not affected by treatment with dapson,

may not detectable after teatment with gluten

free diet

• Immunoelectron Micrc: IgA associated with

bundles of microfibril, anchoring fibrils of the

papillary dermis below the basal lamina

Immunogenetic FindingsImmunogenetic Findings

• 77%-87% : HLA-B8

• Class II major histocompatibility complex : HLA-DR and DQ associated in DHHLA-DR and DQ associated in DH

HistopathologyHistopathology

• Early lesions (non vesicular)� dermal papillary collections of neutrophils (micro absces), neutrophilic fragments, eosinophil, fibrin� sometimes separation eosinophil, fibrin� sometimes separation of the papillary tips from the overlying epidermis

• Upper and middle dermal blood vessels are suurounded by lymphohistiocyte infiltrate

TreatmentTreatment

• Sulphones: diaminodiphenyl sulfone

(dapsone),

sulfoxone (diasone)

Dose: 100 mg-150 mg/day (once a day)Dose: 100 mg-150 mg/day (once a day)

occasional: 300-400 mg/day, 25 mg/week

Sulphapyridine: 1,0-1,5 gr daily

(in pat. intolerant of dapsone)

3636

Pemphigus VulgarisPemphigus Vulgaris

Pemphigus VulgarisPemphigus Vulgaris

THANK YOU FOR LISTENINGTHANK YOU FOR LISTENINGTHANK YOU FOR LISTENINGTHANK YOU FOR LISTENING