Pierluigi Sapelli

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

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.

Evaluation of environmental bacterial contamination and procedures to control cross infection in a sample of Italian dental surgeries

OBJECTIVES To perform a pilot study on bacterial contamination in some dental surgeries (n=51) in a local health unit in Brescia (Lombardy Region, Italy) and to evaluate the procedures to control cross infection used by the personnel to reduce the risk of infection in dental practice. METHODS A survey was carried out by interviewing 133 dental personnel with a questionnaire on the procedures used to control infection. The autoclaves, chemical baths (chemiclaves), and ovens present in the surgeries were tested for sterilisation efficiency with a spore test, and already packed and sterilised instruments were randomly sampled and tested for sterility. Microbial contamination of air, surface, and dental unit water samples were also studied. RESULTS The dental personnel did not generally follow the principal procedures for infection control: 30% of personnel were not vaccinated against hepatitis B virus, infected instruments were often not decontaminated, periodic checks of autoclave efficiency were lacking, and the knowledge of disinfection mechanisms and procedures was incomplete. High bacteriological contamination of water at dental surgeries was often found and total bacteriological counts in air samples were high. Surface studies showed widespread bacterial contamination. CONCLUSIONS On the basis of these results, an educational programme for the prevention of infective hazards has been prepared and carried out. The results of this pilot study will be used for planning a national survey.

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.

Mechanical response of bone under short-term loading of a dental implant with an internal layer simulating the nonlinear behaviour of the periodontal ligament.

We consider a non-standard design for a fixed dental implant, incorporating a soft layer which simulates the presence of the periodontal ligament (PDL). Instead of being aimed at causing an a priori defined stress/strain field within the surrounding bone, upon loading, such a design simply tries to better reproduce the natural tooth–PDL configuration. To do this, the mechanical properties of the internal layer match those of the PDL, determined experimentally to be strongly nonlinear. Three-dimensional finite element analyses show that the presence of such a layer produces (i) a prosthesis mobility very similar to that of a healthy tooth, for several loading conditions, and (ii) a stress/strain distribution substantially different from that arising, upon loading, around a conventional implant. The lack of knowledge of the real mechanical fields existing, under loading, in the bone around a healthy tooth makes it very difficult to state that the stress distribution produced by the modified implant is “better” than that produced by the standard one. Nevertheless, the comparison of the results obtained here, with those of previous refined analyses of the tooth–PDL–bone system, indicates that the modified implant tends to produce a stress distribution in the bone, upon loading, closer to “natural” than that given by the standard one, within the limits imposed by the presence of threads coupling the implant with the bone.