Chronic Vesikobulosa Dermatosis 1. Pemphigus 2. Bullous Pemphigoid 3. Dermatitis Herpetiformis 4. Chronic Bullous Disease of Childhood 5. Cicatrical Pemphigoid 6. Gestationes Pemphigoid 7. Bullous Epidermolysis

Pemphigus Pemphigus: a group of Autoimmune blistering diseases of the skin & mucous membranes characterized intra epidermal blisters due to acantholysis (separation of epidermal cells from each other)

Classification 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

Immunopathologically Bound and circulating IgG directed against the cell surface of keratinocyte P. Vulgaris (PV): blister in the deeper part of epidermis above the basal layer P. Foliaceus (PF)= superficial pemphigus  blister in the granular layer

Immunofluorescense 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 surface of KC in perilesional skin 80%> : pat. PV circulating antiepithelial cell surface IgG

Pemphigus 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 Manifestation Skin: Rarely pruritic often painful Flaccid blister arises on normal appearing skin/ erythematous skin fragile broken blistererosions often painful erosions quite large tendency to spread at their periphery Bulla> vesicles

Clinical Manifestation Nikolsky sign (+): active blister applying lateral pressure to normal appearing skin Erosion excessive granulation tissue & crusting intertrigenous areas scalp, face Mucous membrane: painful m. membrane erosion ( 5 month before skin lesion develop)

Nikolsky sign (+) Pemphigus Epidermolysis Bullosa Erythema Multiforme Toxic Epidermal Necrolysis

Clinical 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 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 cavity basal layer stay attached to the BMZmay lose the contact with their neigbors row of tombstones Bulla : intra epidermal/ supra basal

Tzanck Test To show acantholytic Epidermal cells

Immunofluorescence The hallmark: IgG autoantibodies against the cell surface of keratinocytes Indirect immnunofluorescence: 80 % pats.  have circulating antiepithelial surface IgG

Treatment Prednisone: high dose disease activity is controlled tapering pred. low dose If combination immunosuppressive dose intermediate/ low dose Immunosuppressive: mycophenolate mofetil (cellcept) azathioprine (imuran) cyclophoaphamide (cytoxan)

Bullous Pemphigoid Usually occurs in elderly pat. Mortality 6%-40% in 1 year Pruritic urticarial lesions Tense large blisters Oral m. membrane erosions in minority of pats Direct Immunfluorescence C3 , IgG at epidermal basement membrane

Bullous pemphigoid

Immunofluorescence Direct: C3 and IgG at epidermal basement membrane Indirect: antibasement membrane IgG in serum Perilesional skin reveals immunoreactants deposited in linear pattern at epid basement membrane

Autoantigens Proteins in the Kc hemidesmosome a basal cell-basement membrane adhesion structure

Etiology & pathogenesis Electron microscopy: early blister formation occurs in the lamina lucida, between the basal cell membrane and the lamina densa Blister formation: there is loss anchoring filaments and hemidesmosome degranulation of infiltrating leucocytes

Immunofluorescence Indirect IMF antibodies does not usually correlate with disease extent/ activity in contrast in pemphigus) C3 and other components classicals and alternative complement pathways & complement regulatory protein B 1H at BMZ Activated complement in blister fluid

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

Clinical 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 periphery Localisation: lower abdomen inner / anterior thights flexor forarms/ any where The lesion do not scar

Clinical Finding Usually : pruritus Sometimes: erythematous component pat. with urticarial lesion Resolution : from the center, hyperpigmentation M. Membrane : 10-35% limited oral MM (buccal mocosa)

Treatment Localized BP: topical steroids topical tacrolimus Extensive disease oral prednisone: 1mg/kg BB/day once a day Topical thy 40 gr/day clobetasol propionate cream 0,05% 2 x/day Immonosupresive: azathioprine

Dermatitis Herpetiformis Characterized by an intensely itchy Chronic papulovesicular eruption Distribution symetrically on extensor surfaces Clearly distinguished from other subepidermal blistering erup. By histologic, immunologic, Gastro Intest Criteria Any age Associated gluten sensitive enteropathy

Etiology and pathogenesis Antibodies to tissue transglutaminases (Tigases) in sera from DH. Epidermal tigase is the dominant autoantigen 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%)

Diagnostic Granular immunoglobulin A deposits in nomal appearing skin Assocated gluten sensitive enteropathy

Clinical Manifestation Primary lesion: erythematous papule urticarial like plaque/ vesicles >> Large bullae occure infrequently Vesicles in palm: hemorrhagic Disappearance : hyperpigmentation & hypopigmentation Herpetiform (herpes like): group of lesions

Clinical Manifestation Symptoms: severe stinging, burning, itching Symetric distribution: 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 Test Perilesional and uninvolved skin pat DH: granular (or fibrillar) Ig deposits located in dermal papilary tips igA IgA deposits are unaffected by treatment with drugs may decrease in intensity or disappear after long term adherence to gluten free diet

Laboratory 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, 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 Findings 77%-87% : HLA-B8 Class II major histocompatibility complex : HLA-DR and DQ associated in DH

Histopathology Early lesions (non vesicular) dermal papillary collections of neutrophils (micro absces), neutrophilic fragments, eosinophil, fibrin sometimes separation of the papillary tips from the overlying epidermis Upper and middle dermal blood vessels are suurounded by lymphohistiocyte infiltrate

Treatment Sulphones: diaminodiphenyl sulfone (dapsone), sulfoxone (diasone) 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)

Pemphigus Vulgaris

Pemphigus Vulgaris

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