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Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.

Candida species are commensal yeasts of the oral cavity, which, under predisposing systemic and/or local circumstances, are responsible for a wide variety of clinical manifestations, globally known as oral candidiasis. Candida-associated denture stomatitis is an oral candidiasis particularly affecting the oral mucosa covered by a dental prosthesis, with several degree of severity. Diabetics suffer oral candidiasis more frequently than healthy individuals do and if they are denture wearers, the risk increases. Since various controversies still remain regarding the interrelationship among diabetes, oral Candida spp. strains involved in denture stomatitis and the presence of dentures, the present review aims to investigate the differences in Candida species frequencies and degree of denture stomatitis severity existing among diabetic and non- diabetic individuals, with and without dentures.

Objective: Aims of this study were to test the efficacy of anti-BP180-NC160 ELISA in the diagnosis of oral pemphigoid compared to the gold standard, represented by direct immunofluorescence and pathological examination, to correlate the antibody titers with the severity of the disease and the demographical data. Materials and Methods: Patients with a suspect of oral pemphigoid were enrolled and underwent biopsy and sera collection both, in order to perform histopathological examination, direct immunofluorescence and ELISA. The test outcomes were compared, and ELISA sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. Results: ELISA showed good specificity (83.3%), while sensitivity was only 50%. A moderate correlation between antibody titers and disease severity was recorded. Conclusions: Mucomembranous Pemphigoid is an autoimmune autoantibody-mediated blistering disease, often affecting exclusively the oral mucosa. Currently, the biopsy is required to diagnose this disease, but serological tests are also commonly employed during clinical practice as adjunctive tools. BP180-NC160 ELISA should be considered an ancillary diagnostic test in course of oral pemphigoid; direct immunofluorescence+histologic examination remains the diagnostic gold standard.

Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway. Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.

Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment. Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment.

Aim To investigate the correlation between the dorsal tongue porphyrin autofluorescence, revealed using VELscope, and Candida saprophytism. Material and methods Consecutive patients underwent an autofluorescence examination by the VELscope device to establish the presence or absence of porphyrin fluorescence. A tongue swab was collected for the Candida cultural test. Sensitivity, specificity, accuracy, negative predictive value and positive predictive value were calculated considering the oral swab as the gold standard. The degree of agreement between the two tests was calculated using Cohen's K coefficient. Results One hundred twenty-six patients were enrolled. Porphyrin fluorescence method showed a sensitivity of 78%, specificity of 76% and an accuracy of 78%. Negative predictive value and positive predictive value were respectively 90% and 59%. The strength of agreement between the two methods resulted to be moderate (k = 0.551). Conclusions Off-label use of tongue autofluorescence examination to detect the presence of Candida species is characterized by a loss of porphyrin fluorescence. The high negative predictive value of porphyrin fluorescence loss suggests its use in preliminary selection of Candida carriers, in order to plan preventive and therapeutic strategies.

Abstract: Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.

Objective: The aim of this study was to test the efficacy of autoantibodies to desmoglein 1 and desmoglein 3 detected by ELISA and indirect immunofluorescence in the diagnosis of oral pemphigus and to correlate the antibody titres with the severity of the disease. Materials and Methods: We report a retrospective cohort study of 22 patients with oral pemphigus and 64 controls from a single tertiary centre. Data about histopathological examination, direct immunofluorescence, indirect immunofluorescence and ELISA were analysed. Global validation of ELISA and IIF both alone and combined was established by calculating sensitivity, specificity, accuracy and both positive predictive value and negative predictive value. The relationship between Oral Disease Severity Score values and ELISA titres was analysed using Pearson's coefficient. Results: The best diagnostic performance was observed for anti-desmoglein 3 ELISA. The sensitivity was 75% and specificity 100% and positive predictive value and negative predictive value were 92.5% and accuracy 93.9%. The level of agreement with histopathology+direct immunofluorescence was substantial (k=.758). Anti-desmoglein 3 titres showed a significant correlation with Oral Disease Severity Score (p&nbsp

Aim: Aim of this case report is to describe oro-facial abnormalities in a patient affected by Helsmoortel-Van der Aa syndrome, a rare autism syndrome, with not well described dental and cranial malformations. Case Report: Helsmoortel-Van der Aa Syndrome is a rare autosomal genetic syndrome causing mental impairment and autism, craniofacial dysmorphism, chest deformity and multiple organs dysfunction. Oro-facial involvement in Helsmoortel-Van der Aa syndrome has not been thoroughly described yet. The present article reports a case of a 9 years old male patient affected by Helsmoortel-Van der Aa Syndrome, presenting with oral breathing typical facies, high arched palate, II class and dental crowding. The patient teething was adequate to his age. The enamel of incisors and molars showed demineralization areas and dark spots, a clinical picture consistent with molar incisor hypomineralization syndrome. These hypo-mineralized areas are more susceptible to cavities, in fact the patient’s 4.6 tooth was decayed. The child was brought to our attention due to a mucocele on the lower lip, confirmed by histopathologic examination. Available data on oro-dental manifestation of this syndrome are rather poor and inconsistent, also due to the rarity of the disease. The finding of enamel abnormalities in the presented case could suggest a potential genetic etiopathogenesis linked to the same genes causing Helsmoortel-Van der Aa syndrome.

Down syndrome (DS) is an autosomal disorder associated with mental and physical involvement. The typical craniofacial phenotype and the dental anomalies in DS subjects have been widely described, but a systematic report on the manifestations affecting the oral mucosae in children with DS is still lacking. This systematic review aimed to establish the prevalence of oral mucosal manifestations in children/young adults with DS. Pubmed, Web of Science, and Scopus were investigated in September 2020. Documents in English on DS children/young adults (up to 25 years) reporting oral mucosal findings were considered. Study quality was assessed with ROBIN-I. Of the 150 references retrieved, 14 studies were considered eligible. The risk of bias ranged from low to unclear. Fissured tongue appeared to increase with age and was more prevalent in DS children than in the general population. Lip fissures and cheilitis were heterogeneously reported. Candida spp. carriage with and without active candidiasis was more frequent in DS children/young adults than in controls. C. albicans was the most prevalent species. Few other oral mucosal conditions have been reported sporadically. The heterogeneity of the works revealed the need for more appropriate oral examination to intercept the oral manifestations of oral mucosa and prevent recurrent candidiasis.

Background: Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases. Materials and Methods: Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors. Results: This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research. Conclusion: Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis. Background: Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases. Materials and Methods: Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors. Results: This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research. Conclusion: Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis.

Objective: The Early Childhood Oral Health Impact Scale (ECOHIS) is a questionnaire to elucidate the relationship between parental perception of the quality of life of their preschool children and their oral health status. Aim of the present work was to validate an Italian ECOHIS version and review the literature. Methods: After adapting the original ECOHIS questionnaire from English to Italian (I-ECOHIS), I-ECOHIS was administered to parents of children afferent to the Dental Clinic of the University of Campania “Luigi Vanvitelli,” regardless of age. Children under 6years of age underwent anamnestic survey and physical examination, to correlate the dmft index with the ECOHIS score. Results: 366 children have come to our observation. I-ECOHIS was administered to all parents to establish its comprehensibility. 87 children (44 females and 43 males) under 6years (5.2±1.4years) underwent dmft evaluation to determine I-ECOHIS/oral health status correlation. Among the 87 children examined, the higher total score reached was 25/50. ANOVA analysis confirmed statistically significant correlations between ECOHIS score and dmft=0 vs dmft equal/higher than 4. Conclusion: The present pilot study validated the I-ECOHIS questionnaire and revealed to be a good tool to distinguish children without caries experience from those with a high dmft. However, it was not correlated with the intermediate dmft level, thus confirming the importance of screening for caries.

Aim: The aim of the present study was to evaluate the prevalence of HPV infection in oral leukoplakia, specifying the HPV genotypes eventually involved. We also compared the micro-biopsy and brushing HPV detecting efficacy. Materials and methods: Consecutive patients with a presumptive diagnosis of oral leukoplakia were enrolled. Demographical, behavioral data (smoking, alcohol) and lesion features were recorded. Each patient underwent a brushing procedure, performed with a cytobrush rubbed on the lesion, and then a biopsy was performed. The brushing and micro-biopsy specimens were both analyzed with the HPV 28 Anyplex II Seegene RT-PCR. The prevalence of HPV infection was calculated considering the two methods’ outcomes separately and then combining both. Cohen’s k coefficient was used to assess the agreement between the two methods. Results: Sixty-five patients were enrolled with a mean age of 60 years. The HPV infection prevalence was 17%, decreasing to 5% considering the brushing outcomes alone. The most frequently detected genotypes were 6 (12%), 11 (3%), 42 (3%), and 16 (3%). No statistically significant correlation was found between HPV infection and the variables analyzed, except for smoking and the type of mucosa (p < 0.05). The strength of agreement between cytobrush and micro-biopsy was “fair” (k = 0.384). Conclusions: The present study showed a low prevalence of HPV infection in oral leukoplakia. The micro-biopsy appeared to be more reliable than brushing in detecting HPV DNA in oral leukoplakia, but the method invasiveness discourages its employ as a screening tool. The importance of HPV in the etiopathogenesis of oral potentially malignant lesions remains unclear; further studies are needed to establish the HPV role in oral leukoplakia. Clinical relevance: HPV involvement in oral leukoplakia and an effective and appropriate detecting technique are still a debated issue. From this study, the restricted use of brushing did not appear sufficient to assess the presence of HPV infection with PCR techniques in samples obtained from oral leukoplakia.

In vivo Reflectance Confocal Microscopy (RCM) allows to optically biopsy vital tissues, non-invasively and in real time. It results in horizontal virtual slices at a microscopic resolution and correlating with conventional histopathology. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by erosive-ulcerative diseases, thus highlighting in vivo the well-known histological peculiarities. A series of conventionally diagnosed Recurrent Aphthous stomatitis (RAS) and Pemphigus Vulgaris (PV) erosive and/or ulcerative oral lesions underwent RCM imaging to establish the application of RCM imaging to this kind of inflammatory non-tumoral lesions. A total of 12 RAS-related lesions and 8 PV-related lesions were considered. RCM imaging was capable to visualize their microscopic peculiarities, mainly inflammatory infiltrate, vessel dilation (RAS) and acantholytic cells, intraepithelial clefts and inflammatory cell carpets (PV). Despite RCM may result unnecessary to diagnose oral lesions referred to RAS and PV, its capability to highlight their main microscopic features could be advantageously used to monitor the healing or worsening of the clinical situation as well as the responsiveness/refractoriness to therapy.

Objectives: Optical coherence tomography (OCT) is a non-invasive technique based on optical imaging with a micrometre resolution. The purpose of this study is to investigate the potential role of OCT in evaluating oral mucosa bullous diseases. Methods: two patients with bullous pemphigoid (BP) and one patient with pemphigus vulgaris (PV) were examined and images of their oral lesions were performed using OCT. Results: In OCT images, the BP blister has a clearly different morphology from the PV one compared to the blistering level. Conclusion: This exploratory study suggests that the OCT is able to distinguish epithelial and subepithelial layer in vivo images of healthy oral mucosa from those with bullous diseases, assisting the clinicians in differential diagnosis.The presented data are in accordance with the scientific literature, although a wider pool of cases is needed to increase statistical power. Histological examination and immunofluorescence methods remain the gold standard for the diagnosis of oral bullous diseases. In this context, the OCT can provide the clinician with a valuable aid both as an additional diagnostic tool and in the follow up of the disease.

Background: West Syndrome is a rare epileptic encephalopathy involving infantile spasms, altered electroencephalographic pattern with hypsarrhythmia, and psychomotor development delay. It arises in paediatric patients, generally within the first year of life, in symptomatic or idiopathic form depending on the presence of hereditary features or not. Case report: In this report it is described the case of a West syndrome patient affected by multiple caries, gingival enlargement, dental eruption abnormalities, high-arched palate and MIH, treated at the dental clinic of University of Bari “Aldo Moro”. Discussion: West patients present with multiple oral abnormalities, including altered eruption timing, teeth agenesis, teeth shape and position abnormalities, plaque and calculus accumulation, malocclusions and bad oral habits (mouth breathing, nails biting). Conclusion:: West Syndrome patients’ oral hygiene is generally bad due to their motor difficulty and to their low compliance towards dentists, which entails general anaesthesia to perform dental treatment. West Syndrome pharmacological treatment is usually based on antiepileptic drugs and/or ACTH. These medications are well known for their ability to induce gingival enlargement, increasing the possibility of plaque accumulation and gingivitis development.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia. Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.