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.

IntroductionNatural killer (NK) cells represent a minor population (5%-20%) of peripheral blood lymphocytes that is also present in secondary lymphoid organs, such as spleen, and lymph nodes, as well as in liver, bone marrow, and maternal uterus. [1][2][3] The function of NK cells in humans is regulated by a balance between opposite signals delivered by a set of HLA class I-specific inhibitory receptors and by a number of activating receptors and coreceptors responsible for NK cell triggering. By the combined use of these receptors, NK cells can discriminate between normal HLA class I ϩ cells and cells that have lost the expression of HLA class I molecules as a consequence of tumor transformation or viral infection. [4][5][6][7] Most NK cells in peripheral blood express the CD56 low CD16 ϩ phenotype, whereas the remainders are CD56 high CD16 Ϫ cells. It was proposed that CD56 high NK cells represent a primary source of immunoregulatory cytokines, whereas the CD56 low C16 ϩ subset represents the principal cytotoxic population. 8 During inflammation, viral infection and tumor growth, NK cells are rapidly recruited from the blood into injured tissues. 9-11 NK cell recruitment is governed by integrated signals, which include adhesion molecules and chemotactic factors. CD56 low CD16 ϩ NK cells express both ␤1 and ␤2 integrins, as well as the ligands for E-and P-selectins. In addition to these molecules, CD56 high NK cells also express high levels of L-selectin, a pivotal molecule for the interaction with lymph node high endothelial venules. 12-14 With respect to chemokine receptors, CD56 low CD16 ϩ NK cells express high levels of CXCR1 and CX3CR1. 9,15 By contrast, CD56 high NK cells express CCR7 as well as CCR5 and CXCR3. 8,9,15 It is likely that the different expression profile of adhesion molecules and chemokine receptors between the 2 major blood NK cell subsets is responsible for the preferential migration of CD56 low CD16 ϩ and CD56 high CD16 Ϫ NK cells into inflamed tissues and secondary lymphoid organs, respectively. 16 In fact, the CD56 high CD16 Ϫ NK cell subset although poorly represented in peripheral blood constitutes the only type of NK cells present in secondary lymphoid tissues. 2,3 We have recently identified a novel protein, chemerin, as the natural ligand of the previously orphan receptor ChemR23. 17 ChemR23 exhibits a unique expression profile among leukocyte populations being expressed preferentially by monocyte/macrophages and by immature myeloid and plasmacytoid dendritic cells (DCs). 18 Chemerin, originally isolated from inflamed biologic fluids, such as ovarian cancer ascites and rheumatoid arthritis synovial fluids, is synthesized as a secreted precursor protein.Prochemerin is poorly active but can be rapidly converted into a full ChemR23 agonist by the proteolytic removal of the last 6 amino acids by neutrophil-derived proteases (elastase and cathepsin G), mast cell products (triptase), and proteases of the coagulation cascade. 19,20 Therefore, prochemerin represents a "ready to The online ...

Purpose To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. Results Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration. Conclusions The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.

SummaryBackground An association between hepatitis C virus (HCV) infection and lichen planus (LP) has been investigated, but results have been inconsistent. Objectives To investigate the relationship between LP and HCV seropositivity. Methods In a cross-sectional study we tested the sera of 303 consecutive newly diagnosed patients with histologically proven LP referred to three Italian centres for the presence of anti-HCV IgG. A comparable control group was also tested. Next, in a systematic review, studies were identified by searching different databases in April 2004. Inclusion criteria were: (i) analytical study design; (ii) clinical and histological diagnosis of LP; and (iii) serological test for anti-HCV antibodies as main outcome. The risk of bias was assessed on the basis of characteristics of the study group, appropriateness of the control group and study design. Pooled data were analysed by calculating odds ratios (ORs), using a random effects model. Results In the cross-sectional study, nearly one in five (19AE1%) of the LP group was HCV positive, while a much lower prevalence of infection was found in the control group (3AE2%) [OR 7AE08; 95% confidence interval (CI) 3AE43-14AE58]. The systematic review yielded 25 relevant studies, six of which had a low risk of bias. There was a statistically significant difference in the proportion of HCV-seropositive subjects among patients with LP, compared with controls (OR 4AE80; 95% CI 3AE25-7AE09). Following subgroup analyses, the variability of HCV prevalence in patients with LP seemed to depend on geographical area, but not on age. Conclusions Anti-HCV circulating antibodies are more common in patients with LP than in controls, although such an association may not be significant in some geographical areas.