Chronic Ulcerative Stomatitis (CUS)

Chronic Ulcerative Stomatitis (CUS) is an immune mediated disorder predominately affecting the oral mucosa. The condition was first described by Jaremko, and mimicks erosive oral lichen planus (OLP) in clinical features but associated with an antinuclear autoantibody mostly recognized as a specific immunological marker being the stratified epithelium‐specific antinuclear antibody (SES‐ANA) (1). There have been less than 75 cases of CUS reported in the English literature and in the data available the age of CUS patients ranged from 28 to 86 years (mean age at diagnosis of 62.15 ± 12.3 years) (2).

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The buccal mucosa and the gingiva are the most common site affected and presents with nonspecific painful erosions/ulcers.

Clinical Features ​

  • The buccal mucosa and the gingiva are the most common site affected and presents with nonspecific painful erosions/ulcers. The ulcers may be indistinguishable from the typical lesions of erosive OLP and be surrounded by white striae (3). Gingival lesions manifest in the form of desquamative gingivitis, which is very similar to the clinical appearance of erosive OLP or vesiculobullous diseases (4).

Diagnosis ​

  • CUS often shares some clinical and histopathological features with OLP, lichenoid stomatitis, mucous mem­brane pemphigoid, dermatitis herpetiformis, linear IgA disease, pemphigus vulgaris, erythema multiforme, pyostomatitis vegetans, and epidermolysis bullosa ac­quisita (5). Direct immunofluorescence (DIF) is in lesional and perilesional oral mucosal specimens is indispensable and the gold standard to establish definitive diagnosis of CUS. H & E and serology for indirect immunofluorescence are helpful and supportive of differential diagnosis (2). Recently Azzi et al., 2019, have suggested a major and minor diagnostic criterion for diagnosis of CUS that included DIF and serology test (2)

 

Diagnostic Criteria

  • Major Criteria

    • Clinical features

      • chronic painful erosions and/or ulcerations

    • DIF analysis

      • lgG SES-ANA deposition in the lower third of epithelium with a speckled pattern

  • Minor Criteria

    • Clinical Features

      • Middle-aged or older women

      • Chronic course with relapses

      • Buccal mucosa, tongue (ventral aspect and/or lateral borders), desquamative gingivitis

      • Lichenoid appearance with white striae departing from lesions borders symmetrical distribution

      • Association between diffuse intra-oral distribution and cutaneous lichenoid lesions

    • Histopathology H&E

      • Lichenoid stomatitis, mainly associated with a band-like mixed infiltrate made of lymphocytes and plasma cells

    • IIF Analysis

      • lgG SES-ANA deposition at the basal layer of epithelial substrates (i.e., guinea pig oesophagus) with a speckled pattern

      • Negative results when using HEp-2 or non-epithelial substrates

    • Laboratory Findings

      • 70-kDa protein detected as autoantigen by immunoblotting or other techniques

      • Positive results at ELISA test for anti-∆Np63a antibodies

    • Therapy

      • Failure or only partial response with corticosteroids

      • Response to hydroxychloroquine (at least 200 mg/day) alone or combined with low doses of corticosteroids

  • Diagnosis

    • 2 major criteria or 1 clinical major criterion + 4 minor criteria

      • (1 clinical criterion, 2 between histopathologic, IIF and/or laboratory findings and 1 therapeutic criterion)

Direct Immunofluorescence (IIF) ​

  • Direct IF in CUS demonstrates deposits of IgG with a speckled pattern in the nuclei confined to the basal and parabasal cells (Fig. A) and in some cases deposits of fibrin (Fig. B) in the junctional region with a shaggy appearance extending into the lamina propria. Due to this junctional fibrin deposits similar to lichen planus or lichenoid reactions, these may appear to be lichen planus (1) 

Indirect Immunofluorescence (IIF) ​

  • Indirect IF testing demonstrates circulating stratified epithelium-specific anti-nuclear antibodies (SES-ANA) on monkey esophagus. Stratified epithelial sources from guinea pig or rat esophagus have been reported by some to be more sensitive (1). Complement-fixing SES-ANA on monkey esophagus demonstrates a classic IF pattern principally in the basal and parabasal cell layers (See Fig A). Antinuclear antibodies may also appear on monkey esophagus with or without SES-ANA. Some patients exhibit coexistent ANA others do not.  An ANA on HEp2 cells should also be tested when an ANA appears on monkey esophagus in such patients. SES-ANA may be found in high titers and are directed toward an antigen of about 63 kDa (4). 

Treatment

  • CUS responds better to antimalarials, especially hydroxychloroquine, at doses of 200 mg/day or higher, alone or in combination with corticosteroids to avoid relapses (6). 

Chronic Ulcerative Stomatitis (CUS) Tests

Selected References

  1. Jaremko WM, Beutner EH, Kumar V, Kipping H, Condry P, Condry P, Zeid MY, Kauffman CL, Tatakis DN, Chorzelski TP. Chronic ulcerative stomatitis associated with a specific immunologic marker.  J Am Acad Dermatol 1990; 22:215-220.

  2. Azzi L, Cerati M, Lombardo M, Pellilli M, Croveri F, Maurino V, Tagliabue A, Tettamanti L, Olszewska M. Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria. Oral Dis. 2019 Sep;25(6):1465-1491.

  3. Chorzelski TP, Olezewska M, Jarzabek-Chorzelska M, Jablonska S. Is chronic ulcerative stomatitis an entity? Clinical and Immunological findings in 18 cases. Eur J Dermatol 1998; 8:261-265.

  4. Solomon LW, Chronic ulcerative stomatitis. Oral Diseases2003; 14:383-389.

  5. Alshagroud, R., Neiders, M., Kramer, J. M., & Suresh, L. (2017). Clinicopathologic significance of in vivo antinuclear autoantibodies in oral mucosal biopsies. Oral surgery, oral medicine, oral pathology and oral radiology, 124(5), 475-482.

  6. Islam MN, Cohen DM, Ojha J, Stewart CM, Katz, Bhattacharyya I, Chronic ulcerative stomatitis: Diagnostic and management challenges – four new cases and review of literature.  Oral Surg, Oral Med, Oral Pathol, Oral Radiol Endod 2007;104:194-203.