Objective The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. Subjects and Methods. Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. Results Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). Conclusion The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

Autoimmune bullous diseases are a group of rare, chronic blistering diseases that affects the skin and mucous membranes. Mucous membrane pemphigoid (MMP) is the most frequently occurring autoimmune bullous disease in the oral cavity, followed by pemphigus vulgaris (PV). Early diagnosis of MMP or PV is critical for proper management and prevention of potential serious complications. This study was based on a retrospective review of 39 cases that were classified as MMP (25 patients) or PV (14 patients). Nikolsky's sign characterized by epithelial detachment as a result of slight pressure or rubbing the oral mucosa is a simple test that can confirm the existence of gingival desquamation. A positive reaction was confirmed in 38 patients (97.4%) at their first visit. This result indicates that patients showing positive Nikolsky's sign should include MMP or PV in the differential diagnosis and, in that case, histopathological examination and direct immunofluorescence testing are critical to establish the final diagnosis. For the early diagnosis of autoimmune bullous disorders, oral healthcare providers should consider the use of the test for Nikolsky's sign that may ultimately lead to the early diagnosis of MMP and PV or other diseases or disorders.

Desquamative gingivitis (DG) is characterized by erythematous, epithelial desquama‐ tion, erosion of the gingival epithelium, and blister formation on the gingiva. DG is a clinical feature of a variety of diseases or disorders. Most cases of DG are associated with mucocutaneous diseases, the most common ones being lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris. Proper diagnosis of the underlying cause is important because the prognosis varies, depending on the disease. This chapter presents the underlying etiology that is most commonly associated with DG. The current literature on the diagnostic and management modalities of patients with DG is reviewed.

Early signs and symptoms of autoimmune bullous diseases such as mucous membrane pemphigoid (MMP) or pemphigus vulgaris (PV) develop in the oral cavity in almost all cases. Desquamative gingivitis (DG) is a clinical manifestation common to several diseases or disorders and is frequently associated with autoimmune bullous diseases. This is a retrospective study of 37 patients with MMP (24 cases) or PV (13 cases) including 10 males and 27 females with a mean age of 58.4 years. The study indicates that DG is an early sign of autoimmune bullous diseases such as MMP or PV. About 70.3% of the oral lesions were confined only to the gingiva, and DG was the only manifestation of the diseases. Since some lesions remain limited to the oral cavity for a long period of time, patients diagnosed with MMP or PV should be closely followed because they must be immediately referred to other experts when they develop lesions on parts of their body other than the oral cavity. The oral healthcare provider should collaborate with other healthcare experts including dermatologists, ophthalmologists, and otolaryngologists to evaluate and manage patients with autoimmune bullous diseases in the oral cavity.

AbstractPemphigus vulgaris (PV) is an autoimmune, blistering disease that affects the mucosa and skin. The current theory favors the concept that anti‐desmoglein (Dsg) 3 autoimmunity is the only pathogenic event needed to induce acantholysis. However, a few cases of active PV in the oral cavity had no detectable anti‐Dsg 3 antibody. The aim of this study was to evaluate the differences in clinical and laboratory findings, whether or not the anti‐Dsg 3 antibodies were present. This study was based on a retrospective review of 10 PV cases. The evaluation of the circulating autoantibody titers to Dsg 3 was conducted by using enzyme‐linked immunosorbent assay (ELISA). An index value of 20 or more was used as the cutoff for a positive reaction. Only five of the 10 PV cases had a positive Dsg 3 ELISA. There were no differences in clinical, cytological, histopathological, and direct immunofluorescence findings, whether or not the anti‐Dsg 3 antibodies were present. Of the five patients with a negative reaction at the time of diagnosis, the Dsg 3 ELISA became positive in the follow‐up period in three cases. In the remaining two cases, the Dsg 3 ELISA was consistently negative for 18 months. Dsg 3 ELISA was negative early in some PV cases. Therefore, PV acantholysis may precede the elevation of circulating anti‐Dsg 3 antibody levels. The diagnosis of PV should be considered based on comprehensive clinical, histopathological, and immunofluorescent criteria.

Despite of the ease accessibility of the oral cavity, only ~30% of oral cancer patients are diagnosed at early stages. Some of the factors that contribute to this low rate of early detection are: asymptomatic oral cancer lesions, similarity to benign lesions, and sampling error during biopsy procedures. Progression of oral cancer is accompanied by alterations in the intrinsic fluorescence properties of the oral tissue, making fluorescence lifetime imaging (FLIM) suitable for the diagnosis of oral cancer. In this study, in vivo human oral lesions from 70 patients were imaged using a multispectral FLIM endoscopy system. The collected database consisted of 50 benign lesions, and 20 dysplastic and early stage cancerous lesions, as determined by histopathological diagnosis. For each pixel, three fluorescence decays were collected corresponding to three emission bands (390 nm, 450 nm, 500 nm), and analyzed using a biexponential decay model. Selected parameters of this fitting algorithm along with the normalized intensities at each emission band were used as features for a quadratic discriminant analysis (QDA) classifier. The classification performance was estimated using a 10 fold cross-validation approach, resulting on levels of sensitivity and specificity >85%, and an ROC AUC of 0.9 for detecting dysplastic and cancerous oral lesions from benign lesions. These results demonstrate the potential of endogenous FLIM endoscopy for automated early detection of oral cancer.

A reflectance confocal endomicroscope with double-clad fiber coupler and electrically tunable focus lens is applied to imaging of the oral mucosa. The instrument is designed to be lightweight and robust for clinical use. The tunable lens allows axial scanning through >250 mu m in the epithelium when the probe tip is placed in contact with tissue. Images are acquired at 6.6 frames per second with a field of view diameter up to 850 mu m. In vivo imaging of a wide range of normal sites in the oral cavity demonstrates the accessibility of the handheld probe. In vivo imaging of clinical lesions diagnosed as inflammation and dysplasia illustrates the ability of reflectance confocal endomicroscopy to image cellular changes associated with pathology. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

BACKGROUND AND OBJECTIVE More than 100 salivary constituents have been found to show levels significantly different in patients with oral squamous cell carcinoma (OSCC) from those found in healthy controls, and therefore have been suggested to be potential salivary biomarkers for OSCC detection. However, many of these potential OSCC salivary biomarkers are also involved in chronic inflammation, and whether the levels of these biomarkers could be affected by the presence of chronic periodontitis was not known. The objective of this pilot study was therefore to measure the levels of seven previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and compare them to levels found in patients with OSCC and healthy controls. The seven salivary mRNAs were interleukin (IL)-8, IL-1β, dual specificity phosphatase 1, H3 histone family 3A, ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and spermidine/spermine N1-acetyltransferase 1. MATERIAL AND METHODS Unstimulated whole saliva samples were collected from a total of 105 human subjects from the following four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree, non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and healthy controls. Levels of each mRNA in patient groups (OSCC or chronic periodontitis) relative to the healthy controls were determined by a pre-amplification reverse transcription-quantitative polymerase chain reaction approach with nested gene-specific primers. Results were recorded and analyzed by the Bio-Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs. control groups were analyzed by the Mann-Whitney U-test with Bonferroni corrections. RESULTS Only S100P showed significantly higher levels in patients with OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The difference in S100P levels between patients with OSCC and healthy controls was also marginally significant (p = 0.009). There was no significant difference in the levels of salivary IL-8, IL-1β and dual specificity phosphatase 1 mRNAs between patients with OSCC and patients with CPNS (p = 0.510, 0.058 and 0.078, respectively); no significant difference in levels of salivary ornithine decarboxylase antizyme 1 and spermine N1-acetyltransferase mRNAs between patients with OSCC and patients with CPS (p = 0.318 and 0.764, respectively); and no significant difference in levels of the H3 histone family 3A mRNA between patients with OSCC and either CPS (p = 0.449) or healthy controls (p = 0.107). CONCLUSIONS Salivary S100P mRNA could be a reliable biomarker for OSCC detection, regardless of the presence of chronic periodontitis. The presence of chronic periodontitis could significantly affect the levels of the other six mRNAs, and negatively influence reliability for using them as biomarkers for oral cancer detection.

OBJECTIVE:To evaluate the treatment effect of an antioxidant-essential oil gel on orthodontic patients with generalized gingivitis. The gel contains the essential oils menthol and thymol and the antioxidants ferulic acid and phloretin.MATERIALS AND METHODS:Thirty patients from the university's orthodontic clinic were screened for gingivitis and randomly allocated into treatment and placebo-control groups. Each patient was evaluated at three orthodontic treatment visits (T1, T2, and T3). A periodontal examination, including probing depth (PD), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) was performed at each visit. Between T1 and T2, patients were instructed to apply a topical gel (active or placebo) to their gingiva twice daily after brushing. From T2 to T3, patients were instructed to discontinue use of the gel.RESULTS:The treatment group showed statistically significant (P < .05) reductions of BOP (-13.6 percentage points) and GI (-0.14) between T1 and T2, and significant increases in BOP (13.3 percentage points) and GI (0.14) between T2 and T3. Except for an increase in the GI between T2 and T3, the control group showed no significant changes in BOP or GI over time. The only other significant changes that occurred pertained to the treatment group, which showed significant increases in PD (0.08 mm) and PI (0.18) between T2 and T3.CONCLUSION:Application of a topical antioxidant-essential oil gel is an effective means of reducing inflammation in orthodontic patients with gingivitis.

The 5-year survival rate for oral cancer (66%) is still one of the lowest among major human cancers, and delayed diagnosis until an advanced stage is thought to be the main factor contributing to this low survival rate. The detection and diagnosis of oral cancer is currently based on clinical visual examination and histopathological evaluation of a biopsy specimen. In response to the need for early detection of oral cancer, several diagnostic adjuncts have been developed and sold commercially over the years, including vital tissue staining, brush cytology, light-based visualization adjuncts, and the most recently developed test for salivary biomarkers for oral cancer. The purpose of this article is to review the current knowledge and research regarding these diagnostic adjuncts developed for early detection of oral cancer. Clinicians are best served by an awareness of the advantages and disadvantages of each adjunct, and to always consider and correlate with the clinical findings when interpreting the test results from these adjuncts.

Hiroyasu Endo, Shinichiro Aoki, Takanori Ito, Terry D. Rees, Edward P. Allen, Kayo Kuyama and Hirotsugu Yamamoto

OBJECTIVE:To attempt to establish criteria to differentiate between chronic ulcerative stomatitis (CUS) and oral lichen planus (OLP) with hematoxylin and eosin (H&E) staining alone.STUDY DESIGN:Ten confirmed cases of CUS were reviewed from the Stomatology Clinic at the Texas A&M University Baylor College of Dentistry.RESULTS:The original diagnosis on H&E evaluation was OLP, chronic mucositis, or mucositis with lichenoid features, but subsequent direct immunofluorescence (DIF) revealed a positive speckled intranuclear deposition of immunoglobulin G (IgG) in the basal and parabasal layers of the epithelium, confirming a diagnosis of CUS.CONCLUSIONS:No consistent histopathologic features were present that would allow recognition of CUS from H&E analysis alone. DIF remains the gold standard for diagnosis.

To gather preliminary data concerning the feasibility of using seven salivary mRNAs—IL-8; IL-1β; dual specificity phosphatase 1 (DUSP1); H3 histone family 3A (H3F3A); ornithin decarboxylase antizyme 1 (OAZ1); S100 calcium-binding protein P (S100P); and spermidine/spermine N1-acetyltransferase 1 (SAT1)—for detecting development of oral squamous cell carcinoma (OSCC) in oral lichen planus (OLP) patients and OSCC patients whose disease was in remission.

BACKGROUNDDesquamative gingivitis (DG) is a clinical manifestation common to several diseases. It is known that most cases of DG are caused by mucous membrane pemphigoid (MMP), oral lichen planus (OLP), or pemphigus vulgaris (PV). Early recognition and treatment of these diseases can improve the prognosis, but diagnostic delays are common in patients with DG because obtaining a diagnostic biopsy is technically challenging. A biopsy technique designed to maintain the gingival epithelium for patients with DG was developed. The usefulness of this technique is discussed.METHODSThis study is based on a retrospective review of 27 DG cases. A stab-and-roll technique was used to obtain gingival tissue. This technique is designed to reduce lateral forces on the epithelium during the procedure and to thereby prevent the inadvertent removal of the epithelium from the biopsy specimen. A total of 52 biopsies comprising 27 for hematoxylin and eosin (H&E)-stained samples and 25 for direct immunofluorescence (DIF) testing were reviewed.RESULTSFifty-one of the 52 biopsies (98.1%) maintained the epithelium. Only one biopsy (1.9%) showed that the epithelium was totally absent. Therefore, H&E and DIF features of 51 biopsies were analyzed. Definitive diagnoses of the diseases causing DG included MMP (13 cases), PV (eight cases), and OLP (six cases).CONCLUSIONSA diagnostic biopsy was obtained from the gingiva of patients with DG using the stab-and-roll technique. The gingival epithelium was well maintained, and the relationship with the underlying connective tissue was diagnostic. In the future, this stab-and-roll biopsy technique may facilitate early diagnosis and treatment of diseases causing DG.

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non-invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five-year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up-to-date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon-and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non-cancerous disease activity.

BACKGROUND:Previous research has indicated that salivary interleukin (IL)-6 and IL-8 are potential biomarkers for oral squamous cell carcinoma (OSCC). However, their levels have been found to be significantly elevated in patients with chronic periodontitis (CP) or oral lichen planus (OLP). The data also showed wide variations in levels among the different studies, and no standardization procedure was ever performed. Therefore, the objective of this study is to determine whether CP or OLP confounds the use of IL-6 or IL-8 for OSCC detection.METHODS:Saliva samples were collected from five groups: OSCC before treatment (n = 18); CP (n = 21); disease-active OLP (n = 21); disease-inactive OLP (n = 20); and healthy controls (n = 21). IL-6 and IL-8 concentrations (determined by enzyme-linked immunosorbent assays) were compared, using total salivary protein-standardized levels to validate the data. The Kruskal-Wallis test (α = 0.05) followed by pairwise Mann-Whitney U (post hoc) tests with Bonferroni adjustments (α = 0.00625) were used for statistical analysis.RESULTS:Salivary IL-6 levels were significantly higher in patients with OSCC than in patients with CP (P <0.001), disease-active OLP (P = 0.001), disease-inactive OLP (P <0.001), and healthy controls (P <0.001). Salivary IL-8 levels were significantly higher in patients with OSCC than in patients with CP (P <0.001), but only marginally significantly higher than in healthy controls (P = 0.014). Statistical results of standardized IL-6 and IL-8 levels were consistent with the non-standardized levels in all pairs except one.CONCLUSION:Salivary IL-6 may be a useful biomarker in the detection of OSCC, unconfounded by CP or OLP.

Our thanks to Dr. Rees and Dr. Rossmann for their interest in our article. Unfortunately, as is mentioned in Dr. Hellstein's reply to Dr. Jones, confusion related to our rationale for some of the recommendations may be cleared up by reading the full report referenced in the executive summary. 1 Hellstein JW Adler RA Edwards B et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: recommendations from the American Dental Association Council on Scientific Affairs. www.ada.org/sections/professionalResources/pdfs/topics_aronj_report.pdf Google Scholar We invite all readers to go over that detailed review. ANTIRESORPTIVE AGENTSThe Journal of the American Dental AssociationVol. 143Issue 7PreviewWe read with interest the November JADA article, “Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis: Executive Summary of Recommendations From the American Dental Association Council on Scientific Affairs” (Hellstein JW, Adler RA, Edwards B, et al; for the American Dental Association Council on Scientific Affairs Expert Panel on Antiresorptive Agents. JADA 2011; 142(11):1243–1251 ). Full-Text PDF