Chronic ulcerative stomatitis

Chronic ulcerative stomatitis (CUS) is a recently described condition with specific immunopathologic findings. Demographics indicate that white women in their late middle age are more susceptible to this condition. The clinical history of CUS patients is of painful, exacerbating and remitting oral erosions, and ulcerations. The histologic features are non-specific, with a chronic inflammatory infiltrate, often appearing similar to oral lichen planus (OLP). Diagnosis of CUS requires surgical biopsy with immunofluorescence microscopic examination. Accurate diagnosis is important because the usual treatment option for immunologically mediated diseases, glucocorticoids, is often not effective in treating CUS. However, hydroxychloroquine pharmacotherapy is beneficial in many cases. The lack of awareness of the condition among clinicians and the technical challenges in specimen processing make diagnosis of CUS a challenge, and hence the true prevalence is unknown. Immunofluorescence studies show circulating and tissue-bound autoantibodies to a protein, ΔNp63α, which is a normal component of stratified epithelia. It is unknown if the antibodies are pathogenic, thus the etiology of CUS is also unknown. Studies are needed to elucidate the pathogenesis of CUS, optimize clinical management, and clarify its relationship to OLP and neoplasia.     

ELISA test for p63 antibodies in chronic ulcerative stomatitis

Oral Diseases (2010) 16 , 151–155 Objective: To develop a novel test for chronic ulcerative stomatitis (CUS), a chronic immunologically mediated condition that produces oral ulcerations. Current diagnostic methods require expensive and technically demanding in situ immunofluorescence (IF) studies. Design: An Enzyme‐Linked ImmunoSorbent Assay (ELISA) was prepared and tested with serum samples from patients with CUS and negative controls. Materials and Methods: The N‐terminal portion of the CUS autoantigen, ΔNp63α, was produced as a purified recombinant protein and used to coat ELISA plates. Sera from 25 patients with CUS and 16 negative controls were analyzed for reactive antibodies. The optimal cut‐offs for positive and negative samples were determined. Main outcome measures: The optimal cut‐off of 0.236 resulted in a sensitivity and specificity of the ELISA of 0.80 and 0.75, respectively (exact 95% confidence intervals, P‐value of <0.001). Results: The ELISA developed in this study provides a novel and reliable diagnostic assessment to distinguish CUS from other oral ulcerative diseases. Conclusions: Immunoassay will allow the true incidence and prevalence of CUS to be determined in future studies. When combined with clinical correlations, the ELISA results will facilitate the evaluation of the prognostic utility of antibody titers and allow correlation with treatment responses in individual CUS cases.     

Expression of CD163, interleukin‐10, and interferon‐gamma in oral squamous cell carcinoma: mutual relationships and prognostic implications

Tumor‐associated macrophages (TAMs) and their associated inflammatory cytokines represent the major inflammatory component of the stroma of many tumors and can affect prognosis in the case of neoplasms. The objective of this study was to determine the prognostic significance of CD163⁺ cells, interleukin‐10 (IL‐10), and interferon‐gamma (IFN‐γ) in oral lesions associated with oral squamous cell carcinoma (OSCC). The levels of CD163, IFN‐γ, and IL‐10 in the tissue samples of 240 patients with OSCC and 58 patients with other oral lesions were assessed by immunohistochemistry. Individuals with low IFN‐γ levels, high IL‐10 levels, and low CD163 levels were of special concern with respect to OSCC progression. We found that high levels of CD163, or a combination of low IFN‐γ levels, high IL‐10 levels, and low CD163 levels, were associated with poorer overall survival (OS). CD163⁺ cells provide better predictive power for OS in comparison with traditional markers, such as clinical stage and lymph node metastasis. Therefore, CD163⁺ cells may be effective prognostic predictors of OSCC. IL‐10 may also indicate poor outcomes when IFN‐γ secretion is low and the cells are CD163^?.     

Co‐expression of Hif1α and CAIX is associated with poor prognosis in oral squamous cell carcinoma patients

J Oral Pathol Med (2010) 39 : 313–317 Background: This study investigates the prognostic impact of the expression of hypoxia‐inducible factor 1α (Hif1α) and carbonic anhydrase IX (CAIX) detected by immunohistochemistry in oral squamous cell carcinoma (OSCC). Methods: Statistical analysis of immunohistochemical results with clinical parameters including survival outcomes was performed for 80 OSCC patients. Results: Patients with a low expression of both proteins survived on average 54.8 months, whereas those with an increased expression of Hif1α in their tumors combined with a low expression of CAIX survived on average only 37.6 months (P = 0.026). In multivariate Cox’s regression hazard analysis, again patients with a low expression of Hif1α/CAIX had the best prognosis, whereas patients with increased Hif1α and low CAIX expression carried a 4.97‐fold increased risk of tumor‐related death (P = 0.042). Conclusion: A co‐detection of low Hif1α/CAIX expression is significantly correlated with a better prognosis for OSCC patients, which may have implications for therapy options for these patients.     

Neutral endopeptidase regulates neurogenic inflammatory responses induced by stimulation of human oral keratinocytes with bacterial lipopolysaccharide and nicotine

Neutral endopeptidase (NEP) is present on various epithelial cells and inactivates numerous physiologically active peptides. Neutral endopeptidase may regulate proinflammatory signals in oral mucosal epithelium. However, the function of NEP in oral mucosal epithelium is unknown. The present study investigated the action of NEP upon proinflammatory signals on human oral keratinocytes and the influence of endothelin‐converting enzyme (ECE)‐1, an enzyme similar to NEP, on the functions of NEP. Oral keratinocytes were cultured in medium containing inflammatory inducers [lipopolysaccharide (LPS) and nicotine], NEP inhibitors, and ECE‐1/NEP inhibitors, either alone or in combination. The concentrations of substance P (SP) and interleukin‐1β (IL‐1β) were measured in the supernatant. Additionally, the concentrations of SP and IL‐1β were measured in the supernatant of cells incubated with LPS or nicotine after transfection with NEP small interfering RNA (siRNA). The concentrations of SP and IL‐1β were significantly increased in cells incubated with NEP inhibitors and, to a lesser extent, in cells incubated with ECE‐1/NEP inhibitors, compared with controls (cells incubated with LPS or nicotine alone). The concentrations of SP and IL‐1β in cells transfected with NEP siRNA were significantly augmented compared with controls. In conclusion, the present study demonstrated that NEP down‐regulated the levels of SP and IL‐1β produced from human oral keratinocytes, although ECE‐1 may be partly related to the down‐regulation.