Chronic Ulcerative Stomatitis

Short presentation of chronic ulcerative stomatitis, an immune mediated disorder that causes vesicles and bullae in the oral cavity. At the end of this presentation, there is a comparison of this vesiculobullous disease with pemphigus vulgaris, mucous membrane pemphigoid, and lichen planus and what is needed for a definitive diagnosis between these four diseases.

1. Chronic Ulcerative S tomatitis

2. Learning Objectives Preface Etiology Pathogenesis Clinical features Histopathologic features Immunofluorescence Comparison of the four vesiculobullous diseases

3. Breaking Down the D isease Chronic  long-lasting or constantly reoccurring Ulcerative  excavations of the oral mucous membranes that extends beyond the basal cell layer Stomatitis  open sores caused by a break in the oral mucous membranes that fails to heal

4. Etiology Immune-mediated disorder that affects the oral mucosa Pathogenesis Unclear pathogenic mechanism Autoantibodies against ∆ Np63 α Interrupts maintenance of the epithelial-connective tissue interface

5. Clinical Features Often misdiagnosed Elderly women, late in 6 th decade Waxes and wanes Lesions (ulcers) in gingiva and also in the buccal mucosa and hard palate

6. Desquamative Gingivitis Severity of symptoms Half of patients have it localized to gingiva Also characteristic of Mucous Membrane Pemphigoid , Pemphigus Vulgaris , and Erosive Lichen Planus Pemphigus Vulgaris Erosive Lichen Planus Mucous Membrane Pemphigoid Chronic Ulcerative Stomatitis

7. Clinical Features Ulcers surrounded by patchy zones of erythema and streaky keratosis Heals without scarring Severity of oral lesions usually wax and wanes Rare cutaneous lesions 20% will develop concurrent lichenoid lesions

8. H istopathologic Features First, biopsy the lesion Similar to lichen planus but epithelium is more atrophic Plasma cells and lymphocytes

9. H istopathologic Features Prominent features of the epithelium Atrophy Liquefaction of the basal cell layer Subepithelial clefting

10. Immunofluorescence Direct Immunofluorescence (DIF) Autoantibodies against IgG and nuclei of stratified squamous epithelial cells Speckled pattern Indirect Immunofluorescence Positive for stratified epithelium-specific autoantibodies

11. Treatment Topical and systemic corticosteroids Hydroxychloroquine sulfate Monitoring for retinopathy and periodic hematologic evaluation Improvement or complete healing

12. Summary of Chronic Ulcerative Stomatitis Often undiagnosed Rare autoimmune disease Autoantibodies to ∆Np63 α – nuclei of stratified squamous cells Usually localized to the gingival and buccal mucous membranes Histopathology similar to Lichen Planus Needs direct immunofluorescence for definitive diagnosis Hydroxychloroquine treatment

13. Clinical Features

14. Histopathologic Features

15. Direct Immunofluorescence

16.   Pemphigus Vulgaris Mucous Membrane Pemphigoid Lichen Planus Chronic Ulcerative Stomatitis Clinical Features 4 th – 6 th decade   Vesicles, erosions, and ulcerations on any oral mucosal or skin surface F > M, 6 th – 7 th decade   Primarily mucosal lesions F > M, 5 th – 6 th decade   Oral and/or skin lesions; may or may not be erosive F >M, Late in 6 th decade   Gingival, buccal, and sometimes hard palate mucosal ulceration Histopathologic Features Intraepithelial clefting Subepithelial clefting Hyperkeratosis, Saw-tooth rete ridges, bandlike infiltrate of lymphocytes Infiltrate of lymphocytes and some subepithelial clefting Direct Immunofluorescence Positive, Between squamous epithelial cells Positive, Basement membrane zone Positive, Fibrinogen at Basement membrane zone Positive, Nuclei of squamous epithelial cells Indirect Immunofluorescence Positive Negative (rarely positive) Negative Positive

17. References Newman, Michael, Henry Takei, Perry Klokkevold , Fermin Carranza. Carranza's Clinical Periodontology, 12th Edition . W.B. Saunders Company, 2015. VitalBook file. Chi , Angela, Brad Neville, Douglas Damm , Carl Allen. Oral and Maxillofacial Pathology, 4th Edition . Saunders, 2016. VitalBook file.

18. Acknowledgements I would like to thank Dr. Anne Jones, DDS, for her guidance and example as an instructor. Additional appreciation to Daniel Chitty, Meredith Mosier, and Jacob Woods for this collaborative group effort.

19. Questions?