autoimmune diseases with oral manifestations · oral manifestations ... treatment...
TRANSCRIPT
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Autoimmune Diseaseswith Oral Manifestations
Martin S. Greenberg DDS, FDS RCSEdProfessor EmeritusDepartment of Oral MedicineUniversity of Pennsylvania
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Disclosure Statement
I have no actual or potential conflict of interest
in relation to this presentation.
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Autoimmune Diseases withmajor oral M/F manifestationsLupus ErythematosisSclerodermaDermatomyositisRheumatoid ArthritisSjogrens SyndromeMultiple SclerosisPemphigus Pemphigoid
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PEMPHIGUS
Autoimmune blistering disease mucosa and skin-potentially fatal
Lesion Intraepithelial Highest Incidence - 5TH-6TH decade Hereditary Component-
Eastern European Jewish Ancestry
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PEMPHIGUS VULGARIS
EtiologyIgG autoantibodies directed against:• Desmosomal adhesion glycoprotein• Desmoglein 3 - mucosal lesions• Desmoglein 1 - skin lesions
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PEMPHIGUS
Pemphigus vulgaris- suprabasilar Pemphigus vegetans- variant of PV Pemphigus foliaceus- granular layer Pemphigus erythematosus- variant of PF Paraneoplastic pemphigus Drug related pemphigus
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PEMPHIGUS VULGARIS
Most common form-80%Oral lesions –anti-DSG 3Skin lesions- anti- DSG 1
Loss of cell to cell adhesionACANTHOLYSIS
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PEMPHIGUS VULGARIS -ACANTHOLYSIS
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PEMPHIGUS VULGARIS
Major Clinical Manifestations Skin-thin walled blisters- lesion intraepithial Mucosa- shallow ulcers pealing mucosa No inflammation Positive Nikolsky sign- manual pressure causes new
lesion
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PEMPHIGUS VULGARISOral Manifestations 90% of all patients 60% - oral lesions precede skin lesions Shallow ulcers Irregular borders Noninflamed based Desquamative gingivitis
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PEMPHIGUS VULGARIS
Diagnosis1) Biopsy - routine histology - suprabasilar
acantholysis2) Biopsy - direct immunofluorescence3) Serum - indirect immunofluorescence
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Pemphigus VulgarisDirect IF Study
Take from clinically normal mucosa Place in Michel’s medium Fluorescein-labeled IgG Pemphigus- IgG binds to surface of keratinocytes
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Pemphigus Vulgaris - Direct Immunofluorescence
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Pemphigus Indirect IF Study Serum placed over mucosa (monkey esophagus) Overlay with fluorescein- tagged anti-Ig Detect ab intercellular ab with fl microscope. Titers used to diagnose PV and monitor disease
activity
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Pemphigus DiagnosisELISA
Enzme linked immunosorbant assay Assay levels of desmoglein 1 and 3 More sensitive than IIF
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PARANEOPLASTIC PEMPHIGUS
Associated with neoplasm Lymphoma Chronic lymphocytic leukemia Thymoma
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PARANEOPLASTIC PEMPHIGUS
Clinical Manifestations1) Severe blistering, erosions, plus inflammation2) Severe oral lesions3) Severe conjunctival lesions4) Respiratory lesions
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Drug-Induced Pemphigus
Major Causes:penicillamine- tx heavy metal toxicity,
rheumatoid arthritiscaptopril- antihypertensive ACE inhibitorAfter dx of --r/o drug induced pemphigus
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PEMPHIGUS VULGARISTreatment Corticosteroids-systemic, topical Immunosuppressive drugs: azathioprine,
mycophenolate, cyclophosphamide Rituxumab-Monoclonal ab CD20-depletes B cells Intravenous Ig (IVIG) Plasmapheresis
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MUCOUS MEMBRANEPEMPHIGOID
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SUBEPITHELIAL BULLOUS DERMATOSES - STOMATITIS
Mucous membrane pemphigoid Bullous pemphigoid Linear IgA disease Chronic bullous dermatosis of childhood Epidermolysis bullosa acquisita
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MUCOUS MEMBRANE PEMPHIGOID
PATHOPHYSIOLOGY Defect in immune regulation Formation of autoantibodies against
protein in basement membrane zone: BP-230, BP-180, laminin, type XVII collegen
Triggers inflammation in BMZ Separation of epithelium from connective tissue
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MUCOUS MEMBRANE PEMPHIGOID
PATHOPHYSIOLOGY
Antibody lamina lucida – BP 180
Antibody lamina densa- epiligren
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ANTI-EPILIGRINMMPRelationship to Cancer Many reported cases
- lung cancer - GI cancer - Gyn cancer - lymphoma
Cancer onset within 15 mos of MMP
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MUCOUS MEMBRANE PEMPHIGOID
Increased in patients over 50 Increased in women Increased cancer risk
Anti-epiligrin (Laminin 5) type
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Mucous Membrane Pemphigoid
ORAL MANIFESTATIONS Oral lesions in 90% Desquamative gingivitis Ulcers and shallow erosions Vesicles and bullae
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MMP Gingiva 20 (100%) Buccal mucosa 13 (65%) Palate 11 (55%) Tongue 5 (25%) Conjunctiva 3 (15%) Vagina 2 (10%) Nasal mucosa 2 (10%) Esophagus 1 (5%)
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LICHEN PLANUS—IDIOPATHICLICHENOID CONTACT REACTIONSLICHENOID DRUG REACTIONSLICHENOID GRAFT VS. HOST DISEASE (GVHD)
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LICHEN PLANUSCLINICAL TYPES
RETICULAR-Wickham’s straie
Plaque Erythematous Erosive(Ulcerative, Bullous)
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Reticular
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Plaque
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LICHEN PLANUSEROSIVE/ULCERATIVE
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LP VS. LUPUS
Routine histology may be similar Use 2nd biopsy-direct I.F.
-lupus band test-( IgG, IgM, C’ at dermal-
epidermal junction)
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ORAL LICHEN PLANUS AND SQUAMOUS CELL CARCINOMA
0.2% to 3% of L.P. patients develop oral cancer 50X increase in risk
(Same as smokeless tobacco)
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