Alessandra Majorana

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome

&NA; Burning mouth syndrome is a common disorder that frequently affects women in the 5th–7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two‐thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two‐thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co‐localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub‐papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small‐fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients.

Recruitment of dendritic cells in oral lichen planus

Using immunohistochemistry the presence of different dendritic cell (DC) subsets was analysed in 16 biopsies from patients with oral lichen planus (OLP). A significant increase of CD1a+/Langerin+ Langerhans cells, DC‐SIGN+ DC and CD123+/BDCA2+ plasmacytoid DCs (PDCs) was found in the epithelium and in the stroma of OLP biopsies compared to normal oral mucosa. A proportion of DCs were mature DC‐LAMP+ and expressed S100 or CD11c, typically found in the interdigitating DCs of nodal T‐cell areas. Double staining revealed that mature DCs co‐expressed CCR7, thus indicating the development of a nodal migratory phenotype upon maturation. Significant recruitment of PDCs producing IFN‐α was demonstrated by the expression of MxA within the lichenoid inflammatory infiltrate and close cell‐to‐cell contacts between PDCs and mature DCs were observed, with a significant correlation between the numbers of these two populations. Moreover, PDCs were also found to contain Granzyme‐B, an associated‐cytotoxic granule protein, inducing target cell apoptosis. Taken together, these results suggest that PDCs may promote maturation of DCs and amplify the cytotoxicity of lymphoid cells. Finally, the recruitment of different subtypes of DC, such as Langerhans cells, stromal DC‐SIGN+ DCs and PDCs, associated with a significant proportion of mature DCs, acquiring a CCR7+ ‘migratory’ phenotype, indicate that they may play a pivotal role in the development of the lichenoid inflammatory infiltrate that occurs typically in OLP. Copyright

Narrow band imaging and high definition television in evaluation of oral and oropharyngeal squamous cell cancer: a prospective study.

Narrow band imaging (NBI) is an optical technique in which filtered light enhances superficial neoplasms based on their neoangiogenic pattern. The accuracy of NBI can be augmented by combining it with high definition television (HDTV). The aim of this study was to prospectively assess the diagnostic value of NBI in combination with HDTV in evaluation of oral (O) and oropharyngeal (OP) squamous cell carcinoma (SCC). Between April 2007 and December 2009, we analyzed 96 patients who were divided into 2 groups: Group A included 35 patients previously biopsied and diagnosed with OSCC or OPSCC and subjected to pre- and intraoperative HDTV white light (WL) and HDTV NBI endoscopy; Group B included 61 subjects already treated for OSCC or OPSCC and followed-up with HDTV WL and HDTV NBI. Fourteen of 35 (40%) patients in Group A showed adjunctive findings with NBI compared to standard WL. All of these findings were histologically confirmed. Twelve of 61 (20%) patients in Group B showed positive NBI findings, which were all confirmed by histology. The sensitivity, specificity, positive, negative predictive values, and accuracy for HDTV WL were 51%, 100%, 100%, 87%, and 68%, respectively, whilst for HDTV NBI were 96%, 100%, 100%, 93%, and 97%, respectively. Overall, 26 of 96 (27%) patients had a diagnostic advantage in applying NBI and HDTV: 6 patients received a diagnosis of recurrence and 1 of persistence after previous treatments; 5 showed a metachronous tumour; in 4 a synchronous tumour was diagnosed; 9 lesions were upstaged; in 1 patient previously diagnosed with an unknown primary by fine needle aspiration cytology on the neck, an anterior tonsillar pillar cancer was identified.

NF‐κB expression in oral and cutaneous lichen planus

Lichen planus (LP) is a chronic inflammatory disorder involving cutaneous and mucosal surfaces, characterized by a T‐cell‐mediated immune response against epithelial cells, with persistent accumulation of T lymphocytes and epithelial cell damage. The mechanisms involved in this chronic inflammatory disease are largely unknown. A pivotal role in the pathogenesis of long‐lasting inflammatory processes is played by the activation of nuclear factor kappa B (NF‐κB), a primary transcription factor which upon translocation to the nucleus, binds to promoter regions of different genes encoding immune and pro‐inflammatory mediators. Using immunohistochemistry, the present study analysed the expression of NF‐κB in 25 cases of cutaneous LP (CLP) and 28 cases of oral LP (OLP) and correlated this with the recruitment of cytotoxic T‐cells (expressing Tia‐1 or perforin) in the inflammatory infiltrate. Nuclear NF‐κB was expressed on basal and suprabasal keratinocytes in all cases of LP, while normal epithelium was consistently negative; OLP contained significantly higher numbers of NF‐κB‐positive keratinocytes than CLP (means: 89.32 versus 22.6; p < 0.05). Furthermore, nuclear NF‐κB expression by epithelial cells correlated with the amount of cytotoxic cell infiltration (p < 0.02). These data suggest that increased NF‐κB activity may represent the basis of maintenance of the inflammatory response. The differences observed between NF‐κB expression on epithelial cells in OLP and CLP and their correlation with the degree of cytotoxic inflammatory infiltrate might explain the different clinical courses of the two variants of the disease, since OLP is typically more recalcitrant than CLP. As proposed for other chronic inflammatory disorders associated with increased NF‐κB activity, the involvement of NF‐κB in the pathogenesis of LP could be considered for selective therapeutic inhibitory targeting. Copyright

Cytotoxic Molecule Expression and Epithelial Cell Apoptosis in Oral and Cutaneous Lichen Planus

We evaluated the expression of T cell-restricted intracellular antigen (Tia-1), granzyme B, and perforin by lymphocytes and the degree of epithelial apoptosis in oral and cutaneous lichen planus (LP) in 51 untreated cases, including 27 oral LP (OLP) and 24 cutaneous LP (CLP) cases. The number of total dermal-positive lymphocytes in OLP and CLP was similar, indicating similar activity of the inflammatory process. Intraepithelial Tia-1-positive, perforin-positive, and granzyme B-positive lymphoid cells were more numerous in OLP than in CLP (P < .05). The epithelial cell apoptotic index (AI) was increased significantly in OLP (P < .05), particularly in erosive-atrophic variants. A linear correlation between AI and the mean +/- SEM number of intraepithelial and dermal perforin+ cells (6.85 +/- 2.44 and 27.48 +/- 10.19, respectively), per 10 high-power fields for OLP and for CLP (1.17 +/- 0.88 and 10.42 +/- 5.74, respectively), was found (intraepithelial, r = 0.50; dermal, r = 0.51; P < .01). These data suggest a pivotal role for perforin in triggering epithelial cell apoptosis. The differences of infiltrating cytotoxic cells and related AI observed in OLP and CLP are in keeping with the clinical behaviors that distinguish these LP variants.

Oral complications of pediatric hematopoietic cell transplantation: diagnosis and management

Abstract Oral complications are a significant cause of morbidity and potential mortality for children undergoing hematopoietic cell transplant (HCT). Oral complications can occur at all stages of HCT and can interfere significantly with transplant recovery. Mucosal disease caused by conditioning regimen toxicity and infection are frequent clinical problems. Untreated dental caries and periodontal disease may result in severe infections of the mouth and/or life-threatening systemic spread of the microbial pathogens. In the course of chronic graft-versus-host disease (GVHD), which can complicate HCT, lichenoid and ulcerative lesions of the mucosa are observed. Furthermore, total-body irradiation utilized in the conditioning regimens can cause early xerostomia and consequent dental decay and also result in significant dental and skeletal developmental anomalies. The dental health care team should have a key role in the support of HCT patients. The teams primary responsibilities are those related to the prevention of severe infections originating in the mouth, which includes providing instruction on oral prophylaxis and hygiene as well as direct intervention. Prevention and/or diagnosis and management of oral complications of HCT by the dental team can improve the success of a transplant by reducing morbidity, improving the quality of life, and reducing the cost of care. The authors present specific protocols for the diagnosis and prevention and for the management of oral complications in pediatric HCT.

Oral mucosal lesions in children from 0 to 12 years old: ten years' experience

OBJECTIVE The exact prevalence of oral lesions in childhood is not well known. We sought to define the prevalence of oral mucosal lesions in a large group of children. STUDY DESIGN A retrospective cross-sectional study was performed using clinical charts from January 1997 to December 2007. Data collected included age, gender, and pathologic diagnosis. RESULTS In total, 10,128 children (0-12 years old) were enrolled. Clinical diagnostic criteria proposed by the World Health Organization were followed. The frequency of children presenting oral mucosal lesions was 28.9%, and no differences related to gender were observed. The most frequent lesions recorded were oral candidiasis (28.4%), geographic tongue and other tongue lesions (18.5%), traumatic lesions (17.8%), recurrent aphthous ulcerations (14.8%), herpes simplex virus type 1 infections (9.3%), and erythema multiforme (0.9%). Children suffering from chronic diseases had a higher frequency of oral lesions compared with healthy children (chi-square: P < .01). CONCLUSION Mucosal alterations in children are relatively common, and several oral disorders are associated with underlying medical conditions.

Dentinogenesis imperfecta in children with osteogenesis imperfecta: a clinical and ultrastructural study

AIM The aim of this study was to assess the correlation between osteogenesis imperfecta (OI) and dentinogenesis imperfecta (DI) from both a clinical and histological point of view, particularly clarifying the structural and ultrastructural dentine changes. DESIGN Sixteen children (6-12 years aged) with diagnosis of OI were examined for dental alterations referable to DI. For each patient, the OI type (I, III, or IV) was recorded. Extracted or normally exfoliated primary teeth were subjected to a histological examination (to both optical microscopy and confocal laser-scanning microscopy). RESULTS A total of ten patients had abnormal discolourations referable to DI: four patients were affected by OI type I, three patients by OI type III, and three patients by OI type IV. The discolourations, yellow/brown or opalescent grey, could not be related to the different types of OI. Histological exam of primary teeth showed severe pathological change in the dentin, structured into four different layers. A collagen defect due to odontoblast dysfunction was theorized to be on the base of the histological changes. CONCLUSIONS There is no correlation between the type of OI and the type of discolouration. The underlying dentinal defect seems to be related to an odontoblast dysfunction.

Burning Tongue and Burning Tip : The Diagnostic Challenge of the Burning Mouth Syndrome

ObjectiveTo investigate the clinical features of burning mouth syndrome (BMS) in a large cohort of patients and to correlate them with the results of tongue biopsy. MethodsWe screened 98 patients complaining of oral burning pain for at least 6 months. Forty-two patients were excluded after screening for contact sensitivity to dental materials, food allergies, tongue injuries, malignancies, connective tissue and metabolic disorders, oral infectious diseases, vitamin deficiencies, and other systemic diseases known to cause neuropathy. Fifty-six patients underwent neurologic examination and assessment of pain intensity, depression, anxiety, quality of sleep, and quality of life. Tongue biopsy with the quantification of epithelial nerve fibers (ENF) was performed in 51 patients. ResultsCompared with 9 healthy participants (4.13±1.85 SD), epithelial innervation density was significantly reduced in 38 patients (1.35±1.46 SD; P<0.0001) and normal in 13 patients (6.1±2.19 SD). The clinical features differed in the two groups: patients with reduced ENF density complained of pain in the whole tongue, lips, hard palate, and alveolar ridges, reported dysgeusia and xerostomia in 29% of cases (P<0.001), and 24% of them were depressed. Patients with normal innervation complained of pain on the tip of the tongue, reported dysgeusia and xerostomia in 7.7% of cases, and 54% of them were depressed (P<0.017). DiscussionThe diagnostic criteria for BMS are not defined yet and the relationship with depression and anxiety is debated. We proposed a biopsy-supported approach for the diagnosis. Our study shows that BMS can present with two distinct clinical pictures and that tongue biopsy can contribute to the assessment of the diagnosis. Mood disorders occur frequently and should be considered when approaching patients and treatment options. These observations could help physicians in identifying patients with BMS and addressing them with the appropriate diagnostic work-up and treatment.

Clinicopathological features and malignant transformation of oral lichen planus: A 12-years retrospective study

Abstract Objective. Oral lichen planus (OLP) is known to be associated with the risk of developing oral squamous cell carcinoma (OSCC). The objective of this study was to investigate the clinicopathological features of OLP and the prevalence of malignant transformation in this setting. Materials and methods. This retrospective study was carried out on 204 medical records of patients with histologically proven OLP who received long-term follow-up (range 6 months–12 years). Data were entered in an informatic database. The statistical analysis, when needed, was performed with the chi-squared test for significance (p < 0.05). Results. At the moment of the diagnosis, out of 204 patients (163 female and 41 male; mean age 54.5 years), 107 patients (52.45%) suffered from systemic chronic diseases, in particular 46 (22.5%) from hepatitis C. Clinically, the reticular form of OLP was the predominant one and most patients had multiple oral sites of involvement. Fourteen patients showed extra-oral lesions. A percentage of malignant transformation less than 1% was found. In fact, two patients (0.98%) underwent a malignant transformation at a site previously diagnosed as OLP. Conclusions. At present, OLP is accepted as being a potential malignant disorder, therefore lifelong follow-up is recommended.