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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.

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.

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.

Background: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease., Methods: Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin., Results: Intra-epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002)., Conclusions: Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.

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 naive lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

Background: Many coeliac disease patients with atypical symptoms remain undiagnosed., Aim: To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis., Patients and Methods: One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed., Results: Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427-4.926) and soft tissue lesions (OR = 41.667, CI = 18.868-90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis., Conclusions: The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low.

Background: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not., Aims: To evaluate the ability of the oral mucosa of patients with CD to produce antibodies in an in vitro culture system., Patients and Methods: Twenty-eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult subjects with other diseases (controls) were studied. All underwent oral mucosa biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium., Results: Sensitivity and specificity of EmA and anti-tTG assayed in the oral mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%, respectively. The CD clinical presentation, such as the presence of oral mucosa lesions, did not influence the results of the EmA and anti-tTG assays in the oral mucosa culture medium. There was an association between positivity of antibodies and greater severity of the oral mucosa lymphocyte infiltration., Conclusion: This study demonstrates that the oral mucosa contributes to EmA and anti-tTG production in untreated patients with CD.