"Burning tongue" and "burning tip": the diagnostic challenge of the burning mouth syndrome.

OBJECTIVE: To 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. METHODS: We 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. RESULTS: Compared 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). DISCUSSION: The 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.

Altered immunolocalization of heat-shock proteins in human peri-implant gingiva.

It has been suggested that heat-shock proteins (HSPs) might be involved in autoimmune disease mechanisms in humans, considering the high degree of sequence homology between bacterial and human HSPs. Several authors have postulated that HSPs might be involved in periodontal disease processes, but not specifically in peri-implantitis. Consequently, using immunohistochemical techniques, we studied the distribution of HSP25, HSP32, HSP60 and HSP72 in three groups of patients: (1) subjects with natural teeth (healthy periodontal tissue), (2) subjects with normal peri-implant mucosa and (3) subjects with clinically evident peri-implantitis. The immunolabelling for HSP25 and HSP60 was increased in the peri-implantitis group HSP32 immunolabelling slightly decreased in peri-implant and peri-implantitis gingiva. Labelling for HSP72 was undetectable in all three groups. In conclusion, we observed in peri-implantitis a clearly enhanced immunolabelling of two specific HSPs, HSP25 and HSP60, restricted to gingival epithelium and this could indicate a signal of local altered homeostasis.

Histochemical and immunohistochemical evaluation of gingival collagen and metalloproteinases in peri-implantitis.

The extra-cellular matrix of the gingival tissue plays an important role in the homeostasis of dental implants. In this work we have studied immunohistochemically the distribution of collagen I-III-IV-V, tenascin, metalloproteinases (MMP) 1-3-8-13 and TIMP-1 in three groups of patients: (1) subjects with natural teeth (healthy periodontal tissue), (2) subjects with normal peri-implant mucosa and (3) subjects with clinically evident peri-implantitis. The immunolabelling for collagen I-III-IV showed a similar pattern in all three groups. The labelling for collagen V increased in lamina propria of healthy peri-implant tissue and peri-implantitis. Tenascin immunolabelling in healthy and peri-implant tissues was scattered in lamina propria. In peri-implantitis tenascin immunolabelling increased mainly near to the basal lamina. The MMP-1-3-8 and TIMP-1 immunolabelling were very faint and localized in the stroma in all three groups. In healthy and peri-implant tissues MMP-13 immunolabelling was found in the lamina propria whereas in peri-implantitis MMP-13 immunolabelling was also in epithelium. On the whole, these data suggest that in the extracellular matrix of peri-implantitis there are alterations of collagen V, tenascin and MMP-13 patterns.

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome.

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-alpha 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.

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.

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.

NF-kappaB 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-kappaB), 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-kappaB 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-kappaB 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-kappaB-positive keratinocytes than CLP (means: 89.32 versus 22.6; p<0.05). Furthermore, nuclear NF-kappaB expression by epithelial cells correlated with the amount of cytotoxic cell infiltration (p<0.02). These data suggest that increased NF-kappaB activity may represent the basis of maintenance of the inflammatory response. The differences observed between NF-kappaB 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-kappaB activity, the involvement of NF-kappaB in the pathogenesis of LP could be considered for selective therapeutic inhibitory targeting.

3.4 Securing the financial future of the university.

The purpose of this paper is to explore current challenges to the financial security of the world's dental schools, analyse and compare current methods of funding dental education, identify best practices and formulate recommendations in order to assist dental educators to meet future fiscal challenges.