1. 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

2. 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)

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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)

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

10. 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)

11. 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

12. Tzanck Test
To show acantholytic Epidermal cells

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

14. 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)

15. 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

16. Bullous pemphigoid

17. 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

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

19. 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

20. 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

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

22. 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

23. 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)

24. 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

26. 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

27. 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%)

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

29. 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

30. 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

31. 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

32. 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

33. Immunogenetic Findings
77%-87% : HLA-B8
Class II major histocompatibility complex : HLA-DR and DQ associated in DH

34. 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

35. Treatment Sulphones: diaminodiphenyl sulfone (dapsone),
sulfoxone (diasone)
Dose: 100 mg-150 mg/day (once a day)
occasional: mg/day, 25 mg/week
Sulphapyridine: 1,0-1,5 gr daily
(in pat. intolerant of dapsone)

37. Pemphigus Vulgaris

38. Pemphigus Vulgaris

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