A personal journey through Oral medicine: The tale of hepatitis C virus and oral lichen planus.

Around 30 years ago, the hepatitis C virus (HCV) was identified and soon it was shown that this virus, further to the liver, could affect a variety of organ systems. This article summarizes how an association between HCV and a relatively common oral disorder, oral lichen planus (OLP), was revealed. Through key publications, many of them published in Journal of Oral Pathology and Medicine, it is shown the building of strong epidemiologic evidence supporting the association and how a plausible pathogenic link between HCV and OLP was discovered. As HCV infection is now potentially curable, modern direct antiviral agents can be used to effectively cure also OLP in HCV-infected patients.

Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers. METHODS: Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels. RESULTS: The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples. CONCLUSION: Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.

Population-based cohort study to assess the gingival lesions in 1319 patients with lichen planus.

AIMS: Oral lichen planus (OLP) is a chronic immune disease. In this paper, we evaluated the overall characters, clinical presentation, and outcome of gingival lesions in OLP Italian patients. METHODS AND RESULTS: A retrospective cohort study was accomplished: a total of 1319 charts were investigated, of whom 922 were female (69.9%): 617 patients (46.8%) manifested white lesions and 702 red ones (53.2%). While most patients had several oral sites of involvement, the gingiva was the unique location in 103 cases. Symptoms were reported in 480 patients (36.4%): 286 patients with erosive OLP, 103 with atrophic form, and 91 with a white form. Long-lasting surveillance showed that only 40 patients (3.03%) had a total clinical signs remission. Regarding OLP medical treatment provided, patients attending less frequently a dental office underwent more often a specific therapy. CONCLUSIONS: To the best of our knowledge, this is the biggest collections of patients with gingival OLP ever described; exclusive gingival lesions are, however, rare and unlikely to undergo a malignant transformation. Moreover, gum lesions seemed to anticipate the appearance of oral lesions and a higher rate of OLP therapy was observed in patients with less frequent dental check-ups and oral hygiene instructions.

Is the early identification and referral of suspected head and neck cancers by community pharmacists feasible? A qualitative interview study exploring the views of patients in North East England.

INTRODUCTION: Head and neck cancer (HNC) is the eighth most common cancer in the United Kingdom. Survival rates improve when the cancer is diagnosed at an early stage, highlighting a key need to identify at-risk patients. This study aimed to explore opportunistic HNC identification and referral by community pharmacists (CPs) using a symptom-based risk assessment calculator, from the perspective of patients with a diagnosis of HNC. METHODS: Purposive sampling was used to recruit patients from the HNC pathway in three large teaching hospitals in Northern England. Qualitative methodology was used to collect data through an iterative series of semistructured telephone interviews. Framework analysis was utilised to identify key themes. RESULTS: Four main themes were constructed through the analytic process: (1) HNC presentation and seeking help; (2) the role of the CP; (3) public perception of HNC and (4) the role of a symptom-based risk calculator. Participants agreed that CPs could play a role in the identification and referral of suspected HNCs, but there were concerns about access as patients frequently only encounter the medicine counter assistant when they visit the pharmacy. HNC symptoms are frequently attributed to common or minor conditions initially and therefore considered not urgent, leading to delays in seeking help. While there is public promotion for some cancers, there is little known about HNC. Early presentation of HNC can be quite variable, therefore raising awareness would help. The use of a symptom-based risk calculator was considered beneficial if it enabled earlier referral and diagnosis. Participants suggested that it would also be useful if the public were made aware of it and could self-assess their symptoms. CONCLUSION: In principle, CPs could play a role in the identification and referral of HNC, but there was uncertainty as to how the intervention would work. Future research is needed to develop an intervention that would facilitate earlier identification and referral of HNC while not disrupting CP work and that would promote HNC and the risk calculator more widely. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement and engagement (PPIE) was integrated throughout the project. Initially, the proposal was discussed during a Cancer Head and Neck Group Experience (CHANGE) PPIE meeting. CHANGE was set up to support HNC research in 2018. The group is composed of seven members (four female, three male) with an age range of 50-71 years, who were diagnosed at Sunderland Royal Hospital. A patient representative from the University of Sunderland PPIE group and a trustee of the Northern HNC Charity were recruited as co-applicants. They attended project management group meetings and reviewed patient-facing documentation.

Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-µg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

A retrospective cohort study reporting rituximab treatment for 33 patients with immunobullous disease.

BACKGROUND: Autoimmune bullous disorders, encompassing pemphigus and pemphigoid diseases, are associated with significant morbidity and mortality. This is in part due to high cumulative doses of corticosteroids in combination with immunosuppressant agents used in traditional treatment regimes. Rituximab is an antiCD20 monoclonal antibody which can induce complete remission, but it is currently unlicensed in the UK and approved only after other treatments have failed. METHODS: We report a retrospective cohort study of 33 patients with pemphigus and pemphigoid diseases treated with rituximab from a single tertiary centre from 2013 to 2019. RESULTS: "Complete remission off therapy" was achieved by 27.3% (n = 9), and a further 27.3% (n = 9) had complete remission on minimal therapy. Twenty-one per cent (n = 7) had "partial remission on minimal therapy"; 9.1% (n = 3) patients were in the "consolidation phase," and 12.1% (n = 4) had a "relapse/flare." A steady reduction in prednisolone doses was observed post-Rituximab infusion. Pre-Rituximab the median dose of prednisolone was 20mg (range 10-35, IQR 25), 15mg (range 9.5-22.5, IQR 13) at 1 month, 9mg (range 5-10, IQR 5) at 6 months, 4mg (range 0-5mg, IQR 5) at 12 months and 0 (0-4.35, IQR 4.25) at 18 months. Twelve per cent (n = 4) of patients had documented infusion reaction symptoms. Twelve per cent (n = 4) had later infective complications. CONCLUSION: This real clinic data adds to the evidence that Rituximab is a safe and effective treatment for both pemphigus and pemphigoid autoimmune blistering conditions. Significantly, we were able to demonstrate a substantial reduction in corticosteroid dosage in our cohort of patients following rituximab treatment.

A service evaluation of the diagnostic testing for mucous membrane pemphigoid in a UK oral medicine unit.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an uncommon bullous disease typically involving the oral cavity. The most commonly used laboratory test for the diagnosis of MMP is direct immunofluorescence (DIF) on fresh perilesional tissue; however, the sensitivity of this test may be hampered by technical difficulties. Immune-serological investigations can also be employed to render a diagnosis. The purpose of this paper was to present an evaluation of diagnostic testing for MMP within an Oral Medicine Unit in UK. METHODS: A retrospective analysis of the medical records was undertaken for patients who had undergone biopsy and DIF testing from January 2016 to December 2018. Parameters analysed included clinical presentation, histopathological features, DIF, salt-split skin indirect immunofluorescence, ELISA anti-BP180 and BP 230 and HLA-DQB1*03:01 findings. RESULTS: Thirty patients (23 females and 7 males, mean age 66.8 years old) were diagnosed with MMP through a combination of histopathology and serological testing. Sixteen patients (53%) were DIF positive, whereas in 14 (47%), MMP diagnosis was achieved using immune-serologic tests. HLA DQB1*03:01 status was undertaken in 15 DIF-positive and 12 DIF-negative patients, and HLA DQB1*03:01 was found in 73% and 58% of the cases, respectively. CONCLUSIONS: This service evaluation has shown that when DIF is informative, it remains the gold standard technique for diagnosis of MMP. However, we have also highlighted the value of serological testing for increasing diagnostic yield for patients with suspected MMP and the potential for HLA DQB1*03:01 as an adjunctive test for the evaluation of MMP.

Value of colchicine as treatment for recurrent oral ulcers: A systematic review.

BACKGROUND: In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, and mouth and genitals ulcers with inflamed cartilage (MAGIC) syndrome. The present review aims to evaluate reliability of colchicine against recurrent oral ulcers. METHODS: A systematic review was conducted, with the following PICO (Patient, Intervention, Control, Outcome) question: "In populations with idiopathic or secondary recurrent oral ulcers, is colchicine more effective in improving pain and accelerating healing, compared to other intervention or placebo?" RESULTS: Seven RCTs and 3 OCTs were considered eligible. Four RCTs focused on BD, two RCTs and three OCTs on RAS, and one RCT on PFAPA syndrome. Heterogeneity between RCTs prevented from meta-analysis. Regarding BD, no significant difference between colchicine and placebo was found in two of three placebo-controlled RCTs, whereas the third RCT showed benefit. A comparative RCT found ciclosporin more effective than colchicine for oral lesions of BD. One open-label RCT showed promising but partial results on colchicine in reducing PFAPA attacks, when compared to corticosteroids. Concerning RAS, colchicine appeared less effective than clofazimine, thalidomide and dapsone, and with outcomes similar to low-dosage corticosteroids but higher gastric discomfort than prednisolone. One OCT reported positive results compared with no treatment but a RCT found no difference with placebo. CONCLUSION: Role of colchicine as treatment for idiopathic or secondary recurrent oral ulcers is still controversial. Further standardized RCTs and crossover trials are needed.

The prompt use of rituximab could decrease adverse effects in patient with pemphigus vulgaris: A preliminary evaluation.

BACKGROUND: The systemic use of corticosteroid is the treatment of choice for patients with pemphigus vulgaris (PV), but adverse effects are frequent. To date, the use of rituximab (RTX) for PV patients is usually indicated when they failed first-line immunosuppressive therapies. The early use of RTX could theoretically lessen adverse effects. METHODS: We performed a single-center study on patients with predominantly oral PV, treated with systemic corticosteroid and the prompt use of 1000 mg of intravenous RTX two weeks apart. We evaluated the clinical response and the reported adverse effect during a period of 24 months, comparing those with a previously published series. RESULTS: The study group comprised 11 patients, while the control group comprised 98 patients. The average time to achieve complete clinical remission was 3.2 ± 2.72 months. Study group took steroids for a mean time of 11.09 ± 2.02 months, and they are all actually disease-free with no medication. Only three patients (27.3%) developed plain side effects. The effect of the length of the corticosteroid therapy on the side effects (also adjusted by sex, age, and clinical oral involvement) was statistically different in the two groups: the prompt use of RTX reduced of 94% the chance to have adverse effects (P = .001). CONCLUSIONS: This is the first report of the use of RTX as first line of therapy for PV patients with predominantly oral involvement. With the proposed regimen, the adverse effects have been minimized compared with classic systemic corticosteroid-centered therapy. Multi-center randomized controlled trail is however necessary.

ROCK1 is associated with non-syndromic cleft palate.

BACKGROUND: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. METHODS: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. RESULTS: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. CONCLUSION: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Interventions for treating oral lichen planus: corticosteroid therapies.

BACKGROUND: Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress. OBJECTIVES: To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication. SELECTION CRITERIA: We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE. MAIN RESULTS: We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution. AUTHORS' CONCLUSIONS: Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.

Oral lichen planus: A disease or a spectrum of tissue reactions? Types, causes, diagnostic algorhythms, prognosis, management strategies.

Oral lichen planus and lichenoid lesions comprise a group of disorders of the oral mucosa that likely represent a common reaction pattern to 1 or more unknown antigens. The coexistence of hyperkeratotic striation/reticulation, varying degrees of mucosal inflammation from mild erythema to severe widespread ulceration, and a band-like infiltrate of mononuclear inflammatory cells including activated T lymphocytes, macrophages, and dendritic cells, are considered suggestive of oral lichen planus and lichenoid lesions. Several classification systems of oral lichen planus and lichenoid lesions have been attempted, although none seem to be comprehensive. In this paper, we present a classification of oral lichen planus and lichenoid lesions that includes oral lichen planus, oral lichenoid contact lesions, oral lichenoid drug reactions, oral lichenoid lesions of graft vs. host disease, discoid lupus erythematosus, and systemic lupus erythematosus, lichen planus-like variant of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, solitary fixed drug eruptions, and lichen sclerosus. We present the clinical and diagnostic aspects of oral lichen planus and lichenoid lesions, and discuss related treatment options.

Botulinum toxin in the management of myofascial pain associated with temporomandibular dysfunction.

INTRODUCTION: Critical evidence on the therapeutic efficacy of botulinum toxins (BTX) is still lacking for most pain conditions. The aim of this review was to evaluate the therapeutic efficacy of BTX in the management of temporomandibular myofascial pain. MATERIALS AND METHODS: Electronic databases PubMed, EMBASE, Scopus, Web of Science, and gray literature were searched for randomized clinical trials until February 2018 to answer a focused question "What is the effectiveness of botulinum toxin in the management of temporomandibular myofascial pain?" Two independent reviewers performed the study selection according to eligibility criteria. RESULTS: A total of seven studies that met the eligibility criteria were included. Two studies showed a significant improvement in temporomandibular myofascial pain, and one study showed equal efficacy of BTX in comparison with facial manipulation, while the remaining studies did not report any significant difference between BTX and control group. Due to heterogeneity in the methodology and outcome assessment, a meta-analysis and recalculation of risk could not be performed. CONCLUSION: Based on our findings, the therapeutic efficacy of BTX was unclear. Randomized controlled trials with better methodological criteria need to be carried out to evaluate the real effectiveness of BTX.

Long-term evaluation of pemphigus vulgaris: A retrospective consideration of 98 patients treated in an oral medicine unit in north-west Italy.

BACKGROUND: Despite the frequency of oral involvement, there are unexpectedly few studies of either on the oral manifestations of pemphigus or their long-term management, and diagnostic delay in Dentistry is frequent. METHODS: We have examined outcome of patients presenting with predominantly oral pemphigus vulgaris (PV). Ninety-eight subjects were followed up for 85.12 months and treated with systemic steroids: 48 of them received adjunctive therapy with azathioprine, 16 with rituximab, 13 with mycophenolate mofetil, three with immunoglobulin and one with dapsone. RESULTS: Clinical remission was achieved in 80 patients (84.21%); 39 of them were off therapy and 41 on therapy. Fifteen patients were not in remission, having been under systemic therapy for 72.16 months. Sixty-nine patients developed detectable adverse effects. Two fatal outcomes were recorded. Each additional year of steroid therapy ensured 47% chance of developing 1 or 2 side effects, and 64% chance of developing more than 3 (ORs 1.47, CI 1.162-1.903; ORs 1.64, CI 1.107-2.130, respectively). CONCLUSION: In one of the largest available cohort with the longest follow-up ever reported, we observed that the management remains need-based and patient-specific, still relying on systemic corticosteroids.

Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.

BACKGROUND & AIMS: There is a close relationship between hepatitis C virus (HCV) infection and lichen planus, a chronic inflammatory mucocutaneous disease. We performed a genome-wide association study (GWAS) to identify genetic variants associated with HCV-related lichen planus. METHODS: We conducted a GWAS of 261 patients with HCV infection treated at a tertiary medical center in Japan from October 2007 through January 2013; a total of 71 had lichen planus and 190 had normal oral mucosa. We validated our findings in a GWAS of 38 patients with HCV-associated lichen planus and 7 HCV-infected patients with normal oral mucosa treated at a medical center in Italy. RESULTS: Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P < 1 × 10-4). We also found an association between a single-nucleotide polymorphism in the HLA-DR/DQ genes (rs9461799) and susceptibility to HCV-associated lichen planus. The odds ratios for the minor alleles of rs884000, rs538399, and rs9461799 were 3.25 (95% confidence interval, 1.95-5.41), 0.40 (95% confidence interval, 0.25-0.63), and 2.15 (95% confidence interval, 1.41-3.28), respectively. CONCLUSIONS: In a GWAS of Japanese patients with HCV infection, we replicated associations between previously reported polymorphisms in HLA class II genes and risk for lichen planus. We also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus, respectively. These genetic variants might be used to identify patients with HCV infection who are at risk for lichen planus.

Current protocols in the management of oral submucous fibrosis: An update.

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF.

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology.

This viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra-epidermal blistering through the "desmoglein (Dsg) compensation" hypothesis, according to which an antibody-dependent disabling of Dsg 1- and/or Dsg 3-mediated cell-cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra-epidermal blistering through the "multiple hit" hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self-repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non-Dsg-specific autoantibodies, and (iii) determine the extent of the contribution of non-Dsg antibodies in disease pathophysiology.

Autoantibody Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and Clinical Involvement.

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6ß4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).

Clinical features and histological description of tongue lesions in a large Northern Italian population.

BACKGROUND: Only few studies on tongue lesions considered sizable populations, and contemporary literature does not provide a valid report regarding the epidemiology of tongue lesions within the Italian population. In this report, the histopathological and clinical appearance of 1.106 tongue lesions from northern Italians are described and discussed. MATERIAL AND METHODS: The case records of patients referred for the diagnosis and management of tongue lesions, from October 1993 to October 2013, were reviewed. Histological data were also obtained and blindly re-examined. RESULTS: For instance, a biopsy performed on a lingual ulcer has a strong predicting association with a carcinoma, whereas a biopsy on a white lesion predicts for a leukoplakia or oral lichen planus. Moreover, a biopsy of erosion is representative of bullous diseases, whereas a biopsy on a verrucous-papillary lesion is significant for fibroma. Furthermore, carcinomas occur in the majority of cases on the lingual edge or pelvis, oral lichen planus is mainly seen on the edge, and fibromas mostly on the lingual tip. CONCLUSIONS: The high frequency of tongue involvement of such different diseases emphasizes the importance of histological characterization and that some diseases occur more frequently than others, with a peculiar clinical aspect and a more common area. In fact our survey can help the clinician in advancing diagnostic hypothesis, on the basis of the elementary lesion and its site of involvement.

Changes in parotid gland morphology and function in patients treated with intensity-modulated radiotherapy for nasopharyngeal and oropharyngeal tumors.

OBJECTIVE: To evaluate the morphological changes of the parotid glands in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal and oropharyngeal tumors and the correlations with parotid function. METHODS: Ten patients with nasopharyngeal and oropharyngeal tumors treated with IMRT between May 2009 and January 2010 at Hokkaido University Hospital were included in this study. In the morphological assessment of the parotid glands, the sizes and computed tomography (CT) numbers of the bilateral parotid glands before and after IMRT with CT were calculated. For functional assessment of the parotid glands, we conducted the Saxon test and used a visual analog scale (VAS) for xerostomia evaluation. RESULTS: Reductions in saliva secretion were observed in the patients treated with IMRT for nasopharyngeal and oropharyngeal tumors, and there was a significant correlation between the reduction in saliva secretion and the VAS. The reductions in the parotid gland size and CT number were larger on the ipsilateral side than on the contralateral side. The reduction in saliva secretion was not significantly correlated with the reduction in parotid gland size, but was significantly correlated with the reduction in CT number. CONCLUSIONS: Morphological and functional changes of the parotid glands were observed after IMRT for nasopharyngeal and oropharyngeal tumors, and preservation of the contralateral parotid glands was only partly achieved. Among the morphological changes of the parotid glands, the CT number may be considered a predictor of parotid function after radiotherapy.