3. To understand how Immunologic vesiculobullous
diseases develop we should be aware of
1. Normal structure of epithelium
2. The pathogenesis of autoimmune diseases
4. To understand how Immunologic vesiculobullous
diseases develop we should be aware of
1. Normal structure of epithelium
2. The pathogenesis of autoimmune diseases
6. Vulgaris
Foliaceus
Erythematous
Vegetans
Circulating B cell mediated autoantibodies of IgG reactive
against epithelial desmosome-tonofilament complexes.
complexes
Protein target:
Desmoglein 3 (Cadherin family) found in basal and lower prickle cells
x
x
7. Vulgaris
Foliaceus
Erythematous
Vegetans
Circulating B cell mediated autoantibodies of IgG reactive
against epithelial desmosome-tonofilament complexes.
complexes
Protein target Desmoglein 3 (Cadherin family)
Genetic and ethnic factors (common in Ashkinazic Jews)
Pathogenesis
1.
Circulating autoantibodies, bound to target antigen
2.
They activates an epithelial intracellular proteolytic
enzymes acting on desmosome-tonofilament complex
3.
Resulting in dissolution & disruption of intercellular
junction and loss of cell to cell adhesion
Autoantibodies
9. Clinical features:
1) Lesions start as short-lived vesicles/bullae that rapidly
rupture leaving ulcers
2) 60% of the lesions start intraorally usually one year before
skin lesions
3) Painful ulceration result in sever debilitation, fluid loss and
electrolyte imbalance,
4) Only Pemphigus vulgaris and P. vegetans (very rare) involve
oral mucosa
5) Common intraoral sites are soft palate, buccal mucosa, floor
of the mouth
6) No sex predilection, common at 4th~5th decades
7) Positive Nikolsky’s sign
10. Histopathological features:
a) Intraepithelial clefting
b) Bullae are suprabasilar
c) Basal layer remain attached to basement membrane
d) Loss of desmosomal attachment result in free floating, or
acantholytic “Tzanc cells”
e) P. foliaceus & P. erythematosus involve upper prickel cell layer
11. Immunopathological features:
a) +ve direct immunoflurescent testing
b) Demonstrates intercellular autoantibodies of
IgG, Complement-3, and less commonly IgA
C3
2014 النثنين 02 يناير
15. Protein target:
Laminin 5 (Epiligrin) Bullous pemphigoid antigen ( BP180)
found in lower part of lamina densa of basement membrane zone
Circulating antibodies have low serum levels undetected in indirect IF
Clinical features:
1)
Affect adults and elderly
2) ♀♂
3)
Vesicles/bullae occasionally rupture leaving
ulcers
4)
Superficial ulcers are painful, with red base.
5)
Chronic, usually heal with scar (Cicatrix)
especially in eye lesions Corneal scaring =
Blindness
6)
Positive Nikolsky’s sign
16. Oral manifestations:
1) Commonly affect
a) Oral Mucosa
c) Conjunctive
b) Larynx
d) Genitalia
2) Routine oral hygiene is oftenly compromised
3) Gingival lesions are bright red (desquamative
gingivitis)
4) Ulcers may affect both marginal and attached
gingiva
17. Histiopathological features:
1) Sub-epithelial bullae
2) Total separation of epithelium from the
connective tissue, So NO acantholysis
3) Inflammation of the underlying
connective tissue
4) Direct IF: IgG C3 deposition in the
basement membrane zone-linear
fluorescent pattern
5) Indirect immunoflurescent only +ve in 5%
18. Protein target:
Laminin Bullous pemphigoid antigen (BP230)+ (BP180)
both synthesized by basal keratinocytes
found in Hemidesmosomes lamina Lucida of basement membrane zone
Circulating antibodies have HIGH serum levels +ve indirect IF
Circulating
auto antibodies
Basement membrane
Attachment complex
Stimulate
Destroy
basement membrane
attachment complex
Complement activation
Attract
Release
lysosomal proteases
2014羟 النثنين 02 يناير
Basement membrane
Neutrophils eosinophils
19. Clinical features:
1) Most common autoimmune blistering condition
2) Age: 60~80 Years
3) Pruritis preceded by or associated with erythema are
the usual early symptom
4) Multiple vesicles that eventually rupture leaving ulcers
5) Ulcers crust with eventual healing without scar
6) Oral lesions affect 1/3 of patients
7) No Sex predilection
8) Positive Nikolsky’s sign
20. Histopathological features:
1)
Separation of epithelium from CT at Lamina
lucida zone= subepithelial separation
2)
Eosinophils exist within the bullae itself
(Characteristic)
Immunopathological features:
1)
Direct immunoflurescent show continuous
linear IgG C3 immuno-reactant band
2)
Antibodies bind to proteins associated with
hemidesmosomes
3)
Indirect immunoflurescent +ve 60~70 %
2014羟 النثنين 02 يناير
21. Etiology and pathogenesis:
a) Cell mediated immunity
b) Role of gluten-sensitive enteropathy (precipitated by the
ingestion of gluten, a component of wheat protein )
Clinical features:
1) Age: young and middle aged adults
2)♂ ♀
3) Chronic disease with characteristic remission and
exacerbation
4) Cutaneous lesions usually herpetiform (aggregated)
i. Papular,
ii. Vesicular
iii. Erythematous,
iv. Intense pruritic rash
1) Affect extensor surfaces (Elbows, shoulders, buttocks)
2) Oral lesions is rare, usually manifested as ulcers involving
both keratinized and non keratinized mucosa surrounded
by erythematous margin
22. Histopathological features:
1) Collection of neutrophils, eosinophils, and fibrin at
papillary tips of dermis
2) Subsequent exudation contribute to epidermal
separation
3) Lymphophagocytic infiltrate is seen in perivascular
spaces
Immunopathological features:
1) Granular IgA deposits at the tips of CT papilla
2) Sometimes we can localize the third component of
complement (C3) in lesional and perilesional tissue
23. Etiology and pathogenesis:
a) Unknown
b) NOT associated with gluten-sensitive enteropathy
(doesn’t respond to dapsone)
Clinical features:
1) Chronic disease of skin
2) Commonly affect mucous membrane
3) Cutaneous lesions usually
i. Urticarial,
ii. Annular,
iii. Targetoid,
iv. Bullous
1) Ocular lesions are common (ulcers)
Histopathological features:
1. Separation at basement membrane
2. Neurtophils and eosinophils fill the separation
2014 النثنين 02 يناير
3. Direct immunoflurescent show linear Ig A deposit at
Epithelium-CT interface
24.
25. Definition pathogenesis:
1.
It is a general term that encompasses one acquired and several
genetic varieties (dystrophical, Junctional, simplex)
2.
Genetically transmitted variety are either (autosomal dominant
autosomal recessive)
3.
Acquired form is called Epidermolysis acquisita, oftenly
precipitated by exposure to specific drugs
Clinical features:
1)
Follow minor trauma over areas of stretch (ex. Elbow knees)
2)
Age
a. Hereditary: infancy and early childhood
b. Acquired: Adulthood
3)
Oral lesions are common severe in recessive form,
uncommon in acquired
i. Bullous, heal with scar
ii. Constricted oral orifice
iii. Hypoplastic teeth
26. Histopathological features:
1) Acquired form:
a) IgG deposits are commonly found in subbasement membrane tissue
b) Collagen VII antibodies located below lamina
densa of basement membrane
2) Hereditary form:
a) Circulating antibodies are NOT evident
b) Pathogenesis related to genetic defects in basal
cells, hemidesmosomes, or anchoring CT
filament
Notas do Editor
MMP: cicatridal pemphigoid, benign mucous membrane pemphigoid, ocular pemphigus, childhood pemphigoid, mucosal pemphigoid, and when it affects gingiva exclusively, gingivosis and desquamative gingivitis.
