Vesiculobullous II

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Oral Pathology I …

Oral Pathology I
Third Year

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  • MMP: cicatridal pemphigoid, benign mucous membrane pemphigoid, ocular pemphigus, childhood pemphigoid, mucosal pemphigoid, and when it affects gingiva exclusively, gingivosis and desquamative gingivitis.


  • 1. By Dr. Wael Mohamed Swelam
  • 2. References
  • 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
  • 5. Immunologic Vesiculo-Bullous diseases Bullous Pemphigoid Mucous membrane Pemphigoid MMP Pemphigus x x Lamina Lucida Lamina densa Linear Immunoglobulin
  • 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
  • 8. Circulating auto antibodies Epithelial cells Stimulate Intracellular proteolytic enzymes Loss of cell/cell adhesion Activate Destruction of desmosome/ tonofilament complex Desmoglein 3 Dissolution & disruption
  • 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
  • 12. Direct immunofluorescence labeled anti-human Ig Fluorescein * Patient’s biopsy (autoantibody in tissue) * +
  • 13. Indirect immunofluorescence Fluorescein labeled anti-human Ig Patient’s serum (with autoantibody ) Control tissue (e.g. normal lip)
  • 14. 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
  • 15. 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
  • 16. 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%
  • 17. 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
  • 18. 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
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. 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
  • 23. 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
  • 24. 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