Autoimmune Diseases with Oral Manifestations
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1 Autoimmune Diseases with Oral Manifestations Martin S. Greenberg DDS, FDS RCSEd Professor Emeritus Department of Oral Medicine University of Pennsylvania
2 Disclosure Statement I have no actual or potential conflict of interest in relation to this presentation.
3 Autoimmune Diseases with major oral M/F manifestations Lupus Erythematosis Scleroderma Dermatomyositis Rheumatoid Arthritis Sjogrens Syndrome Multiple Sclerosis Pemphigus Pemphigoid
4 PEMPHIGUS Autoimmune blistering disease mucosa and skinpotentially fatal Lesion Intraepithelial Highest Incidence - 5 TH -6 TH decade Hereditary Component- Eastern European Jewish Ancestry
5 PEMPHIGUS VULGARIS Etiology IgG autoantibodies directed against: Desmosomal adhesion glycoprotein Desmoglein 3 - mucosal lesions Desmoglein 1 - skin lesions
6 PEMPHIGUS Pemphigus vulgaris- suprabasilar Pemphigus vegetans- variant of PV Pemphigus foliaceus- granular layer Pemphigus erythematosus- variant of PF Paraneoplastic pemphigus Drug related pemphigus
7 PEMPHIGUS VULGARIS Most common form-80% Oral lesions anti-dsg 3 Skin lesions- anti- DSG 1 Loss of cell to cell adhesion ACANTHOLYSIS
8 PEMPHIGUS VULGARIS - ACANTHOLYSIS
9 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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13 PEMPHIGUS VULGARIS Oral Manifestations 90% of all patients 60% - oral lesions precede skin lesions Shallow ulcers Irregular borders Noninflamed based Desquamative gingivitis
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29 PEMPHIGUS VULGARIS Diagnosis 1) Biopsy - routine histology - suprabasilar acantholysis 2) Biopsy - direct immunofluorescence 3) Serum - indirect immunofluorescence
30 Pemphigus Vulgaris Direct IF Study Take from clinically normal mucosa Place in Michel s medium Fluorescein-labeled IgG Pemphigus- IgG binds to surface of keratinocytes
31 Pemphigus Vulgaris - Direct Immunofluorescence
32 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
33 Pemphigus Diagnosis ELISA Enzme linked immunosorbant assay Assay levels of desmoglein 1 and 3 More sensitive than IIF
34 PARANEOPLASTIC PEMPHIGUS Associated with neoplasm Lymphoma Chronic lymphocytic leukemia Thymoma
35 PARANEOPLASTIC PEMPHIGUS Clinical Manifestations 1) Severe blistering, erosions, plus inflammation 2) Severe oral lesions 3) Severe conjunctival lesions 4) Respiratory lesions
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39 Drug-Induced Pemphigus Major Causes: penicillamine- tx heavy metal toxicity, rheumatoid arthritis captopril- antihypertensive ACE inhibitor After dx of --r/o drug induced pemphigus
40 PEMPHIGUS VULGARIS Treatment Corticosteroids-systemic, topical Immunosuppressive drugs: azathioprine, mycophenolate, cyclophosphamide Rituxumab-Monoclonal ab CD20-depletes B cells Intravenous Ig (IVIG) Plasmapheresis
41 MUCOUS MEMBRANE PEMPHIGOID
42 SUBEPITHELIAL BULLOUS DERMATOSES - STOMATITIS Mucous membrane pemphigoid Bullous pemphigoid Linear IgA disease Chronic bullous dermatosis of childhood Epidermolysis bullosa acquisita
43 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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46 MUCOUS MEMBRANE PEMPHIGOID PATHOPHYSIOLOGY Antibody lamina lucida BP 180 Antibody lamina densa- epiligren
47 ANTI-EPILIGRIN MMP Relationship to Cancer Many reported cases - lung cancer - GI cancer - Gyn cancer - lymphoma Cancer onset within 15 mos of MMP
48 MUCOUS MEMBRANE PEMPHIGOID Increased in patients over 50 Increased in women Increased cancer risk Anti-epiligrin (Laminin 5) type
49 Mucous Membrane Pemphigoid ORAL MANIFESTATIONS Oral lesions in 90% Desquamative gingivitis Ulcers and shallow erosions Vesicles and bullae
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61 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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63 LICHEN PLANUS IDIOPATHIC LICHENOID CONTACT REACTIONS LICHENOID DRUG REACTIONS LICHENOID GRAFT VS. HOST DISEASE (GVHD)
64 LICHEN PLANUS CLINICAL TYPES RETICULAR- Wickham s straie Plaque Erythematous Erosive(Ulcerative, Bullous)
65 Reticular
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68 Plaque
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70 LICHEN PLANUS EROSIVE/ULCERATIVE
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80 LP VS. LUPUS Routine histology may be similar Use 2 nd biopsy-direct I.F. -lupus band test- ( IgG, IgM, C at dermalepidermal junction)
81 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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Classification: 1. Infective: 2. Traumatic: 3. Idiopathic: Recurrent Aphthous Stomatitis (RAS) 4. Associated with systemic disease:
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