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Intravenous bisphosphonates (BP) play a key role in the treatment of bone metastases. As a long-term side effects BP, a form of avascular osteonecrosis of the jaw has been reported. Although, invasive oral local procedures are often present in clinical history of patients suffering from bisphosphonates-related osteonecrosis of the jaws (BRONJ), about up to 50% of BRONJ are spontaneous. We report a case of a 68-year-old female with a spontaneous wide bone sequestration of the left mandibular body onset after infusion of zoledronic acid for 18 cycles for osseous metastasis due to metastatic anaplastic thyroidal carcinoma. Surprisingly the clinical aspects of the patient initially reminded us of the famous pathology described in 1899 called phossy jaw. This case is remarkable not only for the spontaneity of the osteonecrosis, but, above all, for the clinical similarity with cases of phossy jaw, described for the first time in the literature, thereby suggesting a potential common pathogenesis.

Introduction: Contrary to early beliefs, celiac disease (CD) is relatively common; however, it still remains underdiagnosed since most cases are atypical, with few or no gastrointestinal symptoms and predominance of extraintestinal manifestations. As a consequence, the diagnosis of the disorder often requires a multidisciplinary approach. Also some oral ailments have been described in celiac patients. In this study, we review the papers that have reported oral manifestations in subjects with CD. Methods: A comprehensive literature search was conducted in Medline and Embase databases using appropriate key words. Additional papers were selected by cross-referencing from the retrieved articles. Results: Dental enamel defects are the oral lesions most closely related to CD. There are conflicting data on the association between CD and recurrent aphthous stomatitis. A correlation of CD with atrophic glossitis has been reported, although robust evidence in support of it is lacking. Patients with CD have caries indexes seemingly lower than healthy individuals, but they may experience delay in tooth eruption. Occurrence of other oral mucosal lesions in CD subjects is likely occasional. Conclusions: Patients with systematic dental enamel defects should be screened for CD even in the absence of gastrointestinal symptoms. CD screening tests for patients with oral aphthae or idiopathic atrophic glossitis should be selectively considered during a medical evaluation that focuses on all aspects of the patient’s status.

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC), the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC (mean age: 62 years, M/F: 2.39∶1) were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included: sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges: dichotomous (≤1 month vs. >1 month) and polytomous (3 months) delay. Data were investigated by univariate and multivariate analyses and a P value ≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were: 'Personal experience of cancer' (dichotomous delay: P=0.05, odds ratio (OR)=0.33, 95% confidence interval (CI)=0.11-0.99; polytomous delay: P=0.006, Chi-square=10.224) and 'Unawareness' (dichotomous delay: P

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Oral mucositis (OM) is a very frequent and potentially severe complication experienced by patients receiving chemotherapy and/or radiotherapy, which often leads to significant morbidity and mortality, and decreased quality of life, and is very costly. Despite its severity and prevalence, there is no standard recognised management today. The aim of this open clinical trial is to evaluate the efficacy and compliance of a new spray compound containing sodium hyaluronate (SH) and a pool of collagen precursor amino acids (AAs) combined with sodium hyaluronate (SH) to manage radio/chemotherapy-induced OM. Twenty-seven consecutive patients with OM were treated according to the manufacturer's instructions. At time TO (baseline — before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0–100) and (ii) severity of OM scored according to WHO Mucositis scale. The treatment efficacy was evaluated on i) pain score, ii) clinical resolution index (CRI) and iii) patient compliance at times T01 (after 2 hours), T1 (after 24 hours), T2 (after 72 hours), T3 (after 7 days) and T4 (after 14 days). Results showed that painful symptoms were significantly reduced after only 2 hours of spray administration compared with baseline measurements ( p

Objectives: Self-injury (SI) is defined as a behavioral disturbance consisting of a deliberate harm to one’s own body without suicidal intent, it is not uncommon and ranges in severity from simple nail-biting to more extreme forms of self-mutilation. The head neck region may be the target of such lesions. SI is associated with several medical conditions, of which it can represent the first clinical sign. Aim of this paper is to describe a series of oral SI, giving special emphasis to the clinical findings, etiology and the management of lesions. Material and Methods: A total of 19 patients with oral SI were prospectively examined; attention was paid to the occurrence and characterization of oral lesions. The management of the lesion also varied depending on the patient medical history, on the etiology of the psychiatric behavior, and on the severity, frequency, and method of inflicting injury. Periodic examinations were performed (after two weeks, three months and six months) and registered. Results: All the patients healed gradually and healing was conditioned by the disease underlying. The treatment consisted of behavior modification in 11 cases, pharmacological treatment in 11 cases, psychotherapy in 2 cases, mouth guard in 9 cases, surgery in 2 cases, extractions in 1 case. Conclusions: Oral SI are uncommon in the clinical practice. They may be associated with a known disease or may be the consequence of this, but often they may be the first sign of a psychiatric disorder. Key words:Oral self-mutilation, self-inflicted lesions, self-injurious behavior, ulcers, Obsessive-Compulsive Disorder, mental retardation.

The oral mucosa offers an interesting site for the application of dosage forms that release drugs within/throughout the oral mucosa, by assuring a high drug bioavailability for topic and systemic effects. However, the relative permeability of the oral mucosa and the washing effect related to the oral fluids and mechanical stresses must be considered in the formulation of oral dosage forms. Since a sustained drug release can be guaranteed only if dosage forms remain in contact with the oral site of absorption/application for a prolonged time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion is a complex phenomenon and the mucoadhesive bond consists of two different parts, the mucoadhesive polymers and the mucous substrate. In addition to factors related to the oral mucosa and oral environment features, the physical-chemical characteristics of mucoadhesive polymers must be also considered as factors influencing the mucoadhesive bonds. While it is not possible to modify the mucosal features or it is possible to modify or inhibit only in part certain mucosal processes, the knowledge of polymer properties influencing mucoadhesive bonds allows to modify or to control these properties in developing increasingly effective mucoadhesive systems. The aims of this review are to discuss the several mechanisms and factors behind the phenomenon of mucoadhesion with particular reference to the features of the oral environment, oral mucosa, and polymeric compounds influencing mucoadhesion process. Finally, a brief mention to the main mucoadhesive dosage forms designed for oral transmucosal drug delivery is made.

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Modern pharmaceutical science has provided us with a wide range of substances to be administered with a wide large variety of dosage forms. Local drug delivery systems have been used for a long time; in particular, for the local therapy of diseases affecting the oral cavity. Although these diseases are often extremely responsive to local therapy, the mouth often presents various difficulties in the application of topical compounds (owing to saliva and the mouth's different functions), resulting in a short retention time of dosage forms with a consequent low therapeutic efficacy. To resolve these limitations, research today concentrates on the development of bioadhesive formulations. This review focuses on the permeability features of oral mucosa, the rationale of oral local drug delivery, and new potential bioadhesive local delivery systems. Furthermore, the most promising mucoadhesive systems proposed to locally treat oral diseases are discussed.

Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell-mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic regimens have been evaluated to treat OLP and pain related, but often without high level of evidence. Topical formulations are the favourite for the majority of cases; bioadhesive formulations have been considered very useful and practical for local drug delivery in oral mucosa, due to the increased residence time on the oral mucosa of the dosage forms and better therapeutic efficacy. In this narrative review, authors try to illustrate the current topical managements for OLP from the accessible literature on this topic. Steroids are very helpful in discomfort and making better quality of life: they are considered the first-line treatment even if they could cause secondary candidosis, and sometimes bad taste, nausea, dry mouth, sore throat or swollen mouth. Other substances or devices by topical administration are adopted especially when the first line approach is refractory. This is the case when retinol with its synthetic and natural analogues (retinoids), hyaluronic acid, or Aloe Vera are chosen. Recent topical applications for OLP therapy include phototherapy and low/high energy pulsing light; the treatment with extracorporeal photochemotherapy is also reasonable and promising. Finally, calcineurin inhibitors (i.e. cyclosporine, tacrolimus and pimecrolimus), antioxidant and biologics (i.e alefacept, efalizumab, basiliximab, TNF-α inhibitors - infliximab, rituximab) may be alternative approaches when OLP does not respond to the standard protocols. In this scenario, there are several studies on molecules different from glucocorticosteroids, but not sufficient or statistically adequate to justify their evidence-based use in OLP; large randomized placebo controlled trials are required to evaluate the safety and effectiveness of these non conventional therapies. In conclusion, since OLP is a chronic disease and requires long-term management, the dental/medical practitioner, who treats OLP patients, needs to know the natural history of OLP, how to monitor, and how to treat, taking in account all of the available modalities conventional and not, with pros and cons.

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Celiac disease (CD) is a lifelong, T cell—mediated enteropathy, triggered by the ingestion of gluten and related prolamins in genetically susceptible subjects, resulting in minor intestinal mucosal injury, including villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient malabsorption. Although serological tests for antiendomysial (EMA) and anti—tissue transglutaminase (anti-tTG) autoantibodies are used to screen and follow up on patients with CD, diagnostic confirmation is still based on the histological examination of the small intestinal mucosa. Although the small intestinal mucosa is the main site of the gut involved in CD, other mucosal surfaces (such as gastric, rectal, ileal, and esophageal) belonging to the gastrointestinal tract and the gut-associated lymphoid tissue (GALT) can also be involved. A site that could be studied less invasively is the mouth, as it is the first part of the gastrointestinal system and a part of the GALT. Indeed, not only have various oral ailments been reported as possible atypical aspects of CD, but it has been also demonstrated that inflammatory changes occur after oral supramucosal application and a submucosal injection of gliadin into the oral mucosa of CD patients. However, to date, only two studies have assessed the capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG antibodies. In this paper, we will review studies that evaluate the capacity of the oral mucosa to produce specific CD autoantibodies. Discrepancies in sensitivity from the two studies have revealed that biopsy is still not an adequate procedure for the routine diagnostic purposes of CD patients, and a more in-depth evaluation on a larger sample size with standardized collection and analysis methods is merited. However, the demonstration of immunological reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA and anti-tTG production, needs to be further evaluated in order to verify whether the oral mucosa is colonized by lymphocytes activated in the intestine or if gluten could stimulate naïve lymphocytes directly in the oral mucosa. This would have important implications for the pathogenesis, diagnosis, and treatment of CD.

Changing demographics, including an increase in life expectancy and the growing numbers of elderly has recently focused attention on the need for geriatric dental care. Ageing affects oral tissues in addition to other parts of the human body, and oral health (including oral mucosa, lips, teeth and associated structures, and their functional activity) is an integral component of general health; indeed, oral disease can cause pain, difficulty in speaking, mastication, swallowing, maintaining a balanced diet, not to mention aesthetical considerations and facial alterations leading to anxiety and depression. The World Health Organization recommends the adoption of certain strategies for improving the oral health of the elderly, including the management and maintenance of oral conditions which are necessary for re-establishing effective masticatory function. Oral health is often neglected in the elderly, and oral diseases associated with aging are complex, adversely affecting the quality of life. Although oral health problems are not usually associated with death, oral cancers result in nearly 8,000 deaths each year, and more than half of these occur at an age of 65 years plus. This report, which is dedicated to geriatric physicians, geriatric dentistry and specialists in oral medicine reviews age-related oral changes in elderly patients and efforts to summarize the effects of aging in hard and soft oral tissues.

Parotid gland metastatic tumours are rare, usually arising from a primary mucosal or cutaneous cancer located in the ipsilateral head and neck region, although metastases from a primary cancer outside the head and neck region are possible. Hepatocellular carcinoma (HCC) rarely metastasizes to the head and neck region and the parotid glands are an even more unusual site. The authors describe the case of an 82-year-old male who presented with a right parotid mass. Percutaneous incisional biopsy with histological and immunohistochemical studies suggested metastatic HCC. Radiological investigations excluded other metastatic lesions. This case illustrates the difficulties that may be encountered when seeking a definitive diagnosis of parotid gland masses and underlines the need for collaboration between clinicians and pathologists when diagnosing a parotid enlargement.

Background Known as “the great imitator,” secondary syphilis may clinically manifest itself in myriad of ways, involving different organs (including the oral cavity), and mimicking, both clinically and histologically, several diseases, thereby making diagnosis a challenge for clinicians. Case report We highlight an interesting case of a 45-year-old man on whose diagnosis of secondary syphilis was based on the presence of unusual oral lesions, consisting of a well delimited, raised, nonhomogeneous, and corrugated white plaque on the right buccal mucosa which mimicked, clinically and histologically, a “leukoplakia-like” plaque and several whitish oral mucous patches localized on the lower labial mucosa and the right lateral margin of the tongue. After the oral lesions, the patient developed a symmetric maculopapular cutaneous rash on the palms, soles, and the trunk of the body. Furthermore, during the anamnesis the patient stated an asymptomatic ulcerative lesion on the glans penis, which had appeared 7 months before the onset of the oral lesions and spontaneously disappeared after 2 weeks. The history of these genital and cutaneous lesions suggested performing serologic tests for syphilis, revealing strongly positive titers and leading us to making a diagnosis of secondary syphilis. Conclusion This case is remarkable because it displays an unusual oral sign, associated with secondary syphilis; in fact, only occasionally does syphilis manifest itself with a “leukoplakia-like” plaque. Dentists should consider secondary syphilis in the differential diagnosis of white and/or ulcerative oral lesions, above all in at-risk patients, given the continuing rise of syphilis in western Europe.

Background Desquamative gingivitis (DG) is a descriptive term used to indicate epithelial desquamation, erythema, erosions, and/or vesiculobullous lesions of the gingiva. DG is commonly associated with several mucocutaneous disorders and systemic conditions that may carry a poor prognosis and high morbidity; however, there are no clear data concerning the frequency of these disease associations. Methods We investigated the epidemiologic features of DG in 125 patients and compared our findings with information from a literature review. Results In our series, 88% of patients with DG had one of the following three disorders: oral lichen planus (OLP), mucous membrane pemphigoid (MMP), or pemphigus vulgaris. The most common cause of DG was OLP (75% of patients). 22% of patients had isolated gingival involvement, and there were diffuse gingival lesions in 57% of patients. Symptoms ranged from none (1%) to severe pain (10%). There was extra-oral involvement of skin in 14% of patients, conjunctiva in 7%, genital mucosa in 26%, and internal organs in 3%. Our study showed MMP to be associated with DG in only a small percentage of patients (9%); this finding may be related to the patient population, epidemiology of the specific disease, and referral and/or past diagnostic bias. Conclusion Based on our series and recent reports, OLP seems to be the most common cause of DG.

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naïve lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

Aims. Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. Methods. A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. Results. Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p = < 0.0001; chi-square = 41.687; odds ratio = 4.3123; 95% confidence interval = 2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p = 0.0003; chi-square = 13.101; odds ratio = 24.67; 95% confidence interval = 2.63:231.441). Conclusions. The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration. (c) 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Objectives The protective role of saliva in the case of oesophageal exposition to gastric acid has long been studied but some contradictions still remain. The main end-point of this study was to evaluate if a qualitative and quantitative alteration in salivary secretion exists in patients affected by GERD. Methods One hundred and twenty patients (T group) with clinically and endoscopically diagnosed GERD, and 98 healthy subjects (C group) have been evaluated; salivary tests (i.e. basal flow rate, stimulated flow rate, pH, [Na + ] and [K + ]) were performed, socio-demographical variables and oral GERD-related symptoms were taken into account. SPSS 10.5 software was used for statistical univariate and multivariate analyses. Results GERD patients and controls were found to have a similar basal flow rate but different stimulated salivary function [T group mean value 0.989 ml/min (±0.48718) vs . C group 1.2197 ml/min (±0.6108), pH [T group mean value 8.935 (±0.471) vs . C group 7.879 (±0.526)] and a higher K + concentration. In GERD patients we also registered a significant association with xerostomia [69/120 (57.5%) vs . 28/98 (28.7%)] and an oral burning sensation [58/120 (48.3%) vs . 19/98 (19.3%)]. Conclusions Our findings assess that salivary secretion is altered in GERD patients and highlight the need for further investigations in order to define the role of saliva in the etiopathogenesis of GERD.

Background A close correlation between celiac disease (CD) and oral lesions has been reported. The aim of this case-control study was to assess prevalence of enamel hypoplasia, recurrent aphthous stomatitis (RAS), dermatitis herpetiformis and atrophic glossitis in an Italian cohort of patients with CD. Methods Fifty patients with CD and fifty healthy subjects (age range: 3–25 years), matched for age, gender and geographical area, were evaluated by a single trained examiner. Diagnosis of oral diseases was based on typical medical history and clinical features. Histopathological analysis was performed when needed. Adequate univariate statistical analysis was performed. Results Enamel hypoplasia was observed in 26% cases vs 16% in controls (p > 0.2; OR = 1.8446; 95% CI = 0.6886: 4.9414). Frequency of RAS in the CD group was significantly higher (36% vs 12%; p = 0.0091; OR = 4.125; 95% CI = 1.4725: 11.552) in CD group than that in controls (36% vs 12%). Four cases of atrophic glossitis and 1 of dermatitis herpetiformis were found in CD patients vs 1 and none, respectively, among controls. Conclusion The prevalence of enamel hypoplasia was not higher in the study population than in the control group. RAS was significantly more frequent in patients with CD.

Direct visualization of the oral tissue autofluorescence has been recently reviewed in several studies as a possible adjunctive tool for early recognition and diagnosis of potentially malignant and malignant oral disorders. The aims of this study were to assess: a) the value of a simple handheld device for tissue auto-fluorescence visualization of potentially malignant oral lesions; and b) the sensitivity, specificity and diagnostic accuracy of tested device, using histological examination as the gold standard. 175 consecutive patients, with at least one clinical oral lesion, were enrolled in the study. Clinical conventional inspections were performed for each patient by two blind operators. Then, oral biopsy and histological examination were performed. Pathologist was blind with respect to the autofluorescence results. The 175 histological assessments revealed no dysplasia, mild dysplasia, moderate/severe dysplasia and OSCC, in the 67.4%, 8.6%, 8%, 16% of cases, respectively. Oral lesions diagnosed as OSCC were found as positive under fluorescent light in the 96.4% of cases. Statistically significant correlation was observed between oral dysplastic lesions and the loss of tissue fluorescence (p-value=0.001). Low sensitivity values (60% and 71%) were recorded about the ability of the device in differentiating mild dysplasia vs. lack of dysplasia and moderate/severe dysplasia vs absence of dysplasia, respectively. The device tested in our study was found to not replace the histopathology procedure. However, we assessed its usefulness for oral tissue examination, especially within an oral medicine secondary care facility, before performing a biopsy and in monitoring oral lesions.