Cutaneous and oral comorbidities in patients with geographic tongue: a multicenter multidisciplinary cross-sectional observational study.

Geographic tongue (GT) represents a localized type of psoriasis inversa and its burden of dermatological and oral comorbidities frequently conditions its severity and diagnosis. Currently, no epidemiological studies have evaluated GT muco-cutaneous comorbidities. We aimed to study oral and dermatological comorbidities in a large sample of GT patients. In this multicenter, cross-sectional study, involving 4 primary referral centers in Italy, we evaluated adult GT patients, who were assessed by board certified dermatologists and dentists for 5 months and collected demographics and medical history. GT was evaluated using Hume's classification together with Geographic tongue severity index (GTASI) to score its severity. The prevalence of oral and dermatological comorbidities was recorded. In the sample we enrolled 137 GT patients (M/F= 5:1) with a mean age of 48,2 ± 14,7 yoa and 33.6% had GT family history. The clinical evaluation found 96 (70.1%) GT type I, 7 (5.1%) type II, 13 (9.5%) type IIIa, 19 (13.9%) type IIIb, 2 (1.5%) type IV, following Hume's classification. The mean GTASI score was 23,7 ± 14,2 and the vast majority displayed a severe form of GT. Eighty-nine patients had oral comorbidities (burning mouth syndrome, caries, parulid and lichen planus) and 80 had dermatological concurrent conditions (plaque psoriasis, inverse psoriasis and atopic dermatitis). In GT patients, both dermatological and dental evaluation should be mandatory to identify previously undiagnosed mucocutaneous comorbidities.

Geographic tongue clinical response in moderate-to-severe psoriatic patients undergoing secukinumab: a real-life, multicenter retrospective observational study.

Geographic tongue (GT), a form of inverse psoriasis, is frequently linked to plaque psoriasis. The objective of the study is to evaluate IL-17 blocker (secukinumab) effect on GT severity. This reallife, multicenter, retrospective observational pilot study evaluated patients with plaque psoriasis and concomitant GT that started in label treatment with secukinumab. Patients were evaluated twice (T0=baseline and T1=after 16 weeks) by a dentist and a dermatologist collecting data on cutaneous Psoriasis Area Severity Index (PASI) and oral statuses using Hume's classification of the Geographic Tongue Severity Index (GTASI). Twenty-nine psoriatic patients with GT treated with secukinumab were enrolled for the study. Seventeen patients display type I GT, 6 type II and 6 type III with an overall GTASI of 25.52±9.57 at the baseline (T0). No correlation was found between delta GTASI and delta PASI (r=-0.27, p=0.1551). GTASI decrement from T0 to T1 was statistically significant ([95%CI -26.64 to -19.56], t=-13.36, p<0.0001). Secukinumab may enter in GT therapeutic armamentarium as the first biologic IL-17 blocker in patients with concomitant moderate-to-severe plaque psoriasis.

Osteogenesis: how can it be stimulated?

Biophysical therapy can be performed using inductive, capacitive, mechanic or implanted devices. The mechanism of action of physical stimuli is at a membrane level where the activation of calcium channels determines the enhancement of cell proliferation and the production of growth factors. Biophysical therapy should be performed using devices and modalities described in the literature. The biophysical stimulation of osteogenesis is effective in the enhancement of the biology of fracture healing in presence of a correct orthopedic treatment in terms of good alignment and stabilization at the fracture site. The choice of which method must be used depends on the segment of bone that has to be treated, the type of fracture and if it is possible to apply the device on the skin. The presence of internal or external fixation devices is not a contraindication.

Liquid biopsy.

During the early formation and growth of primary tumor (e.g., breast, colon, or prostate cancer), cells are shed from the primary tumor and then circulate through the bloodstream. Many of the major recent advances in targeted therapies have relied on the acquisition of tumor tissue via biopsy before initiation of therapy or after the onset of resistance. The advantage of physical properties is that they allow circulating tumor cells separation without labelling. Methods based on physical properties include density gradient centrifugation, filtration through special filters. In addition to using somatic point mutations as markers for the detection of tumor DNA, strategies to detect tumor-derived rearrangements and chromosomal copy number changes in the plasma of patients with cancer have been developed. Several studies have shown that metastatic cells might have unique characteristics that can differ from the bulk of cancer cells in the primary tumor currently used for stratification of patients to systemic therapy. In conclusion, the molecular and functional analysis of circulating tumor cells and circulating nucleic acids can be used as companion diagnostics to improve the stratification of therapies and to obtain insights into therapy-induced selection of cancer cells..

Anti-tumor properties of silver.

The use of silver dates to the period when people used it to mint coins or forge jewels. Towards the end of the 1960s, Resenmberg reported a study on the antitumor activity of cisplatin, and after a few years, cisplatin began to be used all over the world against different types of neoplasias mainly involving testes, ovaries, tumors of the district head-neck. Laryngeal carcinoma cell line HEP2 and tongue carcinoma cell lines PE15 and PE46, were cultured. Cell lines were treated with increasing concentration Ag in order to evaluate the optimal concentration levels that did not significantly affect cell viability. Basing on these data, the concentration adopted for the treatment was 0.007%. Gene expression profile was carried out for 10 genes belong to cell cycle pathways. Significantly up-regulated genes showed ≥ 2-fold change in expression while significantly down-regulated genes showed ≤ 0.5 -fold change in expression. Treatment appears to not significantly affect gene expression in the HEP2 cell line. In fact the only significantly down-regulated gene was CCNE1. All other genes have an expression comparable to that of untreated control. In recent years, the complexes containing gold and silver have been thoroughly studied for their electronic and chemical capabilities and their potential as a valid alternative in the development of new technologies. Further studies on the mechanisms of the biological effect discovered can become fundamental for the development of new high efficiency drugs with minimal minimum effects for the treatment of malignant neoplasia in humans and animals.

Human Papilloma Virus associated with oral cancer and preventive strategies: the role of vaccines.

The aim of this paper is to describe the efficacy of Human Papilloma Virus (HPV) vaccines for preventing oral cancer. A systematic review of the literature was conducted to describe the state of the art about HPV vaccines for preventing oral cancer. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. In recent years there has been a growing interest in HPV in dentistry, suggesting a role of such a family of viruses in the development of oral cancers as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (eg genital, anal and oral). Recent studies about HPV infection are a basic requirement in order to promote the HPV vaccinations and patient’s health.

HPV acting on E-cadherin, p53 and p16: literature review.

In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains uncertain. A systematic literature search was performed using PubMed, Cochrane library, Science Direct, and the Internet search, with language restricted to English. The search included published studies which dealt with detection methods of HPV-related oral and oropharyngeal cancers and biomolecular studies, particularly regarding the compromising of p53 p16 and e-cadherin’s. P53 Tumour suppressor protein p53 has several functions that are related to maintaining genomic stability and inhibiting cell proliferation in response to DNA damage. For preventing neoplasia to occur, the most important of these functions are cessation of cell growth and induction of either apoptosis or senescence. P16 is a cellular protein involved in cell cycle regulation. It is a cyclin-dependent kinase 4 (CDK4) inhibitor, and is integral to Rb mediated regulation of G1-S phase of the cell cycle. P16 is expressed at a very low level in normal cell as Rb inhibits transcription of p16. Various detection methods ranging from immunohistochemistry (IHC) to molecular techniques have been used to determine the HPV status of HNSCC. E-cadherin, a 120 kDa Type I classical cadherin, is expressed primarily on epithelial cells. It is found on the surface of keratinocytesand Langerhans cells (LC) and E-cadherin mediated adhesion between these cell types is required for LC retention in the epidermis. It is also an important tumour suppressor protein: its loss or inactivation is associated with epithelial-to-mesenchymal transition (EMT), a process involving dedifferentiation, infiltration and metastasis of tumours. Oral carcinogenesis is a multi-factorial process involving socioeconomic, environmental and microbial factors leading to multistep changes. Smoking and tobacco exposure seems to modify the survival and recurrence of HPV positive tumours and should be considered in future trials for risk stratification of HPV positive patients. HPV associated oropharynx cancer represents a distinct clinical and biologic entity with many unresolved issues that will be investigated in future translational, clinical research. We need to further explore and understand why the disease occurs predominantly in males, and whether the natural history of oral HPV infection differences in men and women.

The association between burning mouth syndrome and sleep disturbance: A case-control multicentre study.

OBJECTIVES: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. METHODS: In this case-control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analysis, were used. RESULTS: Poor sleep quality (PSQI ≥ 5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p < .001). A depressed mood and anxiety correlated positively with sleep disturbance. The Pearson correlations were 0.570 for the PSQI vs HAM-D (p < .001) and 0.549 for the PSQI vs HAM-A (p < .001). Pain intensity (NRS) poorly correlated to sleep quality; the Pearson correlation was 0.162 for the PSQI vs NRS (p = .021). CONCLUSIONS: The BMS patients showed a poor sleep quality, anxiety and depression, as compared with the controls, highlighting the relationships between oral burning, sleep and mood.

HPV infection in the oral cavity: epidemiology, clinical manifestations and relationship with oral cancer.

PURPOSE: The aim of this paper is to describe epidemiology and clinical manifestations of oral infection by Human papillomavirus (HPV), with particular attention to potential malignant lesions. MATERIALS AND METHODS: A systematic review of the literature was conducted to describe the state of the art about HPV infection in oropharyngeal mucosa and its modalities of transmission, with particular attention to possible simultaneous infection in multiple anatomic sites. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. Therapeutic protocols are also described where necessary. RESULTS: In recent years there has been a growing interest in HPV oral medicine, suggesting a role of such a family of viruses in the development of neoplasms of the oropharyngeal district as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (e.g. genital, anal and oral). CONCLUSIONS: Recent studies about HPV infection are a basic requirement in order to promote the health of patients and provide them with the most exhaustive indications from dentists.

Genetic correlation between rheumatoid arthritis and periodontal disease: the role of sex and IL-10.

The chronic stimulation of the immune system due to the presence of bacterial antigens within periodontal tissues has been associated with several autoimmune diseases, like diabetes mellitus, infective endocarditis or cardiovascular atherosclerosis. The current study aims at evaluating the correlation between Rheumatoid Arthritis (RA) and Periodontal Disease (PD) with special attention to genetic polymorphisms in cytokine expression. A total number of 34 patients affected by RA were recruited. Each of them underwent haematochemical analysis and data were collected for Rheumatoid Factor (RF), Anti-Citrullinated Protein’s Antibody (CCP) and HLA-BDR1. DAS-28 questionnaire for disease activity was fulfilled by the rheumatologist, while a periodontal examination was carried out by the dental clinician and crevicular fluid samples were collected to evaluate the IL-6, IL-10 and VDR polymorphysms. A connection between CCP and IL-10 polymorphisms was found, with IL-10 expressing protecting tendency against periodontal disease when CCP are found in the bloodstream (p=0.0017). Finally, males mainly expressed IL-10 predisposing genes (p=0.046), while females showed a greater tendency to express RF (p=0.014) and CCP (p=0.050). This paper corroborates the idea of a correlation between sex, IL-10 polymorphisms and RA, which should be studied in depth, since recent papers have shown that IL-10 injected into joints seems to decrease inflammation.

A “burning” therapy for burning mouth syndrome: preliminary results with the administration of topical capsaicin.

Burning mouth syndrome is defined as an intraoral burning sensation for which no medical or dental cause can be found. Recently, researchers have demonstrated an altered trophism of the small nerve fibres and alterations in the numbers of TRPV-1 vanilloid receptors. Capsaicin is a molecule that is contained in hot peppers and is specifically detected by TRPV-1 vanilloid receptors that are distributed in the oral mucosae. We aimed at verifying if topical capsaicin could prove to be an effective treatment of Burning Mouth Syndrome. A group of 99 BMS patients were recruited. We subdivided the BMS patients into two groups: the collaborative patients, who expressed a predominantly neuropathic pattern of symptoms, and the non-collaborative patients, who were characterised by stronger psychogenic patterns of the syndrome. Both groups underwent topical therapy with capsaicin in the form of a mouth rinse 3 times a day for a long period. After 1 year of treatment, the final overall success rate was approximately 78%, but with a significant difference in the success rates of the two groups of patients (87% and 20% among the collaborative and non-collaborative patients, respectively; p=0.000). The use of topical capsaicin can improve the oral discomfort of BMS patients, especially during the first month of therapy, but it is more effective for those patients in which the neuropathic component of the syndrome is predominant. Our hypothesis is that chronic stimulation with capsaicin leads to decreases in burning symptoms. This phenomenon is called desensitisation and is accompanied by substantial improvements in oral symptoms.

Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis.

Rheumatoid Arthritis is a disease, which can be described as an autoimmune response after molecular mimicry caused by infective agents. The current study aims at evaluating the correlation between Rhematoid Arthritis (RA) and Periodontal Disease (PD), with special attention to the microbioma detected in the gums. Thirty-four patients with RD were recruited into the current study. Among rheumatic parameters, Rheumatoid Factor (RF), anti-citrullinated protein antibody (CCP), HLA-BDR1 and DAS28 were collected. A dental clinician evaluated the periodontal screening record (PSR). Afterwards, 1 paper cone was inserted for 30 seconds into the gingival sulcus then sent to the laboratory for evaluation. Quantitative PCR of 16S rRNA genes was performed with the hydrolysis probes method to identify and evaluate the amount Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Fusobacterium nucleatum and Campylobacter rectus. There were no statistical differences in the composition of oral microbioma between PSR groups. There were no statistical significant differences between bacterial loads and serum values. On the contrary, a positive correlation was found between the presence of Porphyromonas gingivalis in periodontal pockets on one side and RF and CCP on the other. Therefore, the presence of Porhyromonas gingivalis in periodontal pockets is associated to RA inflammatory indices.

The GOCCLES® medical device is effective in detecting oral cancer and dysplasia in dental clinical setting. Results from a multicentre clinical trial.

The purpose of this study is to demonstrate that the GOCCLES® medical device allows proper autofluorescence examination of the oral mucosa in a dental care setting. This is a non-randomised multicentre clinical trial on consecutive patients at risk for oral cancer. Patients underwent a classical naked eye inspection of the oral cavity followed by autofluorescence examination wearing the GOCCLES® spectacles while the light from a dental curing light irradiated the oral mucosa. Lesions were defined as visible potentially malignant lesions and/or fluorescence loss areas. All persisting lesions underwent excisional or incisional biopsy. Sixty-one patients were enrolled. Data from 64 biopsies were analysed. Of the 62 lesions identified by the device, 31 were true positives. The device identified 31 of 32 true positive lesions. One lesion (an invasive carcinoma) was not visible to the naked eye. The device identified all lesions classified as moderate dysplasia to invasive cancer. In 56.7% of cases, true positive lesions showed greater extension when observed through the device. The GOCCLES® medical device allowed the direct visualisation of fluorescence loss in patients suffering from mild to severe dysplasia and in situ to invasive oral cancer. It allowed autofluorescence examination with each source of light used during the study. These results suggest that the role of the autofluorescence visualisation is that of a complementary inspection following naked eye examination when dealing with patients at risk for oral cancer. The device allows detection of otherwise invisible lesions and otherwise impossible complete resections.

Burning mouth syndrome: the role of contact hypersensitivity.

BACKGROUND: Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions. Some studies have suggested that burning mouth syndrome could be caused by the metals used in dental prostheses, as well as by acrylate monomers, additives and flavouring agents, although others have not found any aetiologic role for hypersensitivity to dental materials. OBJECTIVE: To evaluate the extent and severity of adverse reactions to dental materials in a group of patients with burning mouth syndrome, and investigate the possible role of contact allergy in its pathogenesis. MATERIALS AND METHODS: We prospectively studied 124 consecutive patients with burning mouth syndrome (108 males; mean age 57 years, range 41-83), all of whom underwent allergen patch testing between 2004 and 2007. RESULTS: Sixteen patients (13%) showed positive patch test reactions and were classified as having burning mouth syndrome type 3 or secondary burning mouth syndrome (Lamey's and Scala's classifications). CONCLUSION: Although we did not find any significant association between the patients and positive patch test reactions, it would be advisable to include hypersensitivity to dental components when evaluating patients experiencing intermittent oral burning without any clinical signs.