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Chronic Vesikobulosa Dermatosis Chronic 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
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Chronic Vesikobulosa Dermatosis - ocw.usu.ac.idocw.usu.ac.id/.../emd166_slide_chronic_vesikobulosa_dermatosis.pdf · Chronic Vesikobulosa Dermatosis • 1. Pemphigus • 2. Bullous

Jun 30, 2019

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Page 1: Chronic Vesikobulosa Dermatosis - ocw.usu.ac.idocw.usu.ac.id/.../emd166_slide_chronic_vesikobulosa_dermatosis.pdf · Chronic Vesikobulosa Dermatosis • 1. Pemphigus • 2. Bullous

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

Page 2: Chronic Vesikobulosa Dermatosis - ocw.usu.ac.idocw.usu.ac.id/.../emd166_slide_chronic_vesikobulosa_dermatosis.pdf · Chronic Vesikobulosa Dermatosis • 1. Pemphigus • 2. Bullous

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)

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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

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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

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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

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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

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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

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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)

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Nikolsky sign (+)Nikolsky sign (+)

• Pemphigus

• Epidermolysis Bullosa

• Erythema Multiforme

• Toxic Epidermal Necrolysis• Toxic Epidermal Necrolysis

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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)

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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

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Tzanck TestTzanck Test

• To show acantholytic Epidermal cells

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ImmunofluorescenceImmunofluorescence

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

• Indirect immnunofluorescence:• Indirect immnunofluorescence:

80 % pats. � have circulating

antiepithelial surface IgG

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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)

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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

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Bullous pemphigoidBullous pemphigoid

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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

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AutoantigensAutoantigens

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

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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

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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

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Pemphigoid antigensPemphigoid antigens

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

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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

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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)

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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

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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

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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%)

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DiagnosticDiagnostic

• Granular immunoglobulin A deposits in nomal appearing skin

• Assocated gluten sensitive enteropathy• Assocated gluten sensitive enteropathy

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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

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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

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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

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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

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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

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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

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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)

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Pemphigus VulgarisPemphigus Vulgaris

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Pemphigus VulgarisPemphigus Vulgaris

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