Importance of differential diagnosis of EBV mucocutaneous ulcer and EBV-positive diffuse large B-cell lymphoma: A case report.

RATIONALE: Epstein-Barr virus mucocutaneous ulcers (EBVMCUs) were officially recognized as a clinicopathologic entity in the 2017 revision of the World Health Organization classification, which often occurs in the elderly or in immunosuppressive condition presented as an isolated ulcerative lesion. EBVMCUs are defined as "shallow, sharply circumscribed, mucosal or cutaneous ulcers with underlying polymorphous infiltration." It mostly involves oral mucosa, but some appear in skin or gastrointestinal tract. Typically, patients with EBVMCUs display a slow disease progression and may even undergo spontaneous regression. PATIENT CONCERNS: This report describes the case of a 76-year-old woman who visited our outpatient clinic with the chief complaint of inflammation and ulceration on lower labial, lower right lingual gingiva seemed like acute necrotizing ulcerative gingivitis, and malignancy. DIAGNOSES: She was diagnosed with EBVMCU after tissue biopsy. INTERVENTIONS: Since most oral ulcerations usually appear in nonspecific form, it is important to check thoroughly for any underlying immunosuppressive systemic conditions and laboratory test results in case of viral infection. But she has no remarkable underlying immunosuppressive disorder. OUTCOMES: For this patient, she was initially diagnosed with EBVMCU and showed spontaneous healing, but then relapsed after 4 to 6 months. The patient was re-diagnosed as EBV-positive diffuse large B-cell lymphoma (EBV-positive DLBCLs) after re-biopsy. LESSONS: EBVMCU shows similar symptoms to malignant lesions or acute necrotizing ulcerative gingivitis but shows spontaneous healing. However, in case of EBV-positive DLBCLs, failing to detect and treat the disease in its early stages can lead to a fatal outcome. Thus, this case report highlights the differential diagnosis and appropriate treatment of EBVMCU and EBV-positive DLBCLs.

Chronic Ulcerative Stomatitis (CUS) as an Interdisciplinary Diagnostic Challenge: A Literature Review.

Chronic ulcerative stomatitis (CUS) is a rarely reported disease affecting the oral cavity, most often affecting middle-aged Caucasian females. The aim of the present study is to present the diagnosis, differentiation, and interdisciplinary treatment of this rare disease. CUS is characterized by the presence of an oral erosive or ulcerative lesion. The autoimmune pathogenesis of CUS includes affecting the antigen's activity by DNA-breaking and protein-hydrolyzing enzymes. The stratified epithelium-specific antinuclear antibodies (SES-ANA) are associated with CUS development. Clinically, the lesions presented in oral mucosa might resemble an erosive form of oral lichen planus, whereas gingival lesions seem to be similar to desquamative gingivitis related to dermatological diseases manifested in the oral cavity. Patients often report subjective symptoms related to oral mucosa and general symptoms. Histopathological presentation of CUS is often non-specific and includes sub-epithelial separation from underlying connective tissue, atrophic epithelium, and inflammatory infiltrate with an increased number of plasma cells and lymphocytes. Direct immunofluorescence (DIF) might be used in CUS diagnostics. CUS generally remains nonsusceptible to corticosteroid treatments; however, antimalarial drugs and calcineurin inhibitors are more effective. Further research should be conducted in order to implement a diagnostic protocol and observe the long-term results of CUS management.

Clinical and immunological features of chronic ulcerative stomatitis: A systematic review.

Chronic ulcerative stomatitis (CUS) is a rare disease of the mucous membranes with characteristics similar to other autoimmune diseases. The aim of this study was to conduct a systematic review of the literature to recover all reported cases of CUS in order to summarize what are the clinical, demographic, microscopic, immunological features of CUS and its therapeutic response to different drugs. A systematic review of the literature was carried out following the statements of preferred reporting items for systematic reviews and meta-analyses (PRISMA). The searches were performed in the electronic databases PubMed, Scopus, EMBASE, LILACS, Opengrey, and Google scholar. Inclusion criteria were articles or abstracts reporting at least one case with a final diagnosis of CUS. A total of 696 records were identified through databases, and 25 studies were selected reporting 81 cases. CUS affects more females (92%), and a greater number of cases are reported in Caucasian patients (53%). The age of patients ranged from 20 to 86 years with a mean age of 60 years (±13.86), and 15% of cases reported concomitantly skin lesions. The clinical and histopathological characteristics of CUS are very similar to those of oral lichen planus. The direct immunofluorescence (DIF) remains the gold-standard diagnostic resource and was performed in 69 cases, revealing a dotted pattern of deposition of stratified epithelium-specific antibodies (SES-ANA). The serum of 38 patients was collected for the performance of the indirect immunofluorescence (IIF), and the use of epithelial substrates such as monkey and guinea pig esophagus often resulted in positive SES-ANA IgG. Most patients were treated with antimalarials, and the treatment of choice that proved to be effective is hydroxychloroquine (HCQ). This entity must be considered in the differential diagnosis of other autoimmune diseases, as it may be underreported.

Immunopathogenesis of canine chronic ulcerative stomatitis.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

Clinicopathologic significance of in vivo antinuclear autoantibodies in oral mucosal biopsies.

OBJECTIVE: Although antinuclear autoantibody (ANA) staining of oral biopsy specimens is indicative of chronic ulcerative stomatitis, it is not known whether this staining is characteristic of other autoimmune diseases. Our study was undertaken to characterize the various in vivo ANA patterns detected in the oral mucosa by direct immunofluorescence to describe the associated hematoxylin and eosin findings, and determine whether patients with these findings had a coexisting systemic connective tissue disease. STUDY DESIGN: This was a retrospective analysis of oral biopsy specimens submitted from 2013 to 2016. RESULTS: In vivo ANA staining was present in 72 of the 2019 cases examined. Immunoglobulin G was the most common immunoreactant (71 of 72 cases), and speckled nuclear staining was the most frequent in vivo ANA pattern (52 of 72). In most cases, hematoxylin and eosin staining of biopsy specimens showed mucositis (24 of 34). Detailed clinical information was available for 10 patients, and all of them had an autoimmune disease. CONCLUSIONS: We found similar prevalence of ANA staining with direct immunofluorescence in oral epithelial biopsy specimens as reported for those of skin. In vivo ANA in the oral epithelium may indicate the presence of an immune-mediated disease. Patients who show ANA deposits in oral mucosal biopsy specimens should be investigated for systemic connective tissue disease as well as for chronic ulcerative stomatitis.

Unexpected Acute Necrotizing Ulcerative Gingivitis in a Well-controlled HIV-infected Case.

We herein report the case of a 41-year-old Japanese man with well-controlled HIV who presented with diagnostically difficult acute necrotizing ulcerative gingivitis (ANUG). After diet-induced weight loss, he developed oral pain and disturbance of mouth opening, and was admitted to our hospital. Based on preconceptions of HIV-associated diseases, fluconazole was initiated for candidiasis. However, no improvement was seen and ANUG was finally diagnosed. This case suggests that physicians should consider ANUG in HIV-infected individuals when several risk factors are present, even if CD4+ T-lymphocyte counts have remained stable owing to long-term anti-retroviral therapy.

Necrotising Ulcerative Gingivitis: A Literature Review.

PURPOSE: The literature surrounding necrotising ulcerative gingivitis (NUG) is extensive, yet the rare nature of this disease means that there is a lack of good quality research available. This paper aims to scrutinise the literature and provide an up-to-date summary of the available information. MATERIALS AND METHODS: A literature search was performed electronically using the Cochrane Library, Ovid Medline, Embase, PubMed Clinical Queries and Google Scholar. Keyword searches were carried out, utilising MeSH terms and free text. English language articles primarily were included, with key foreign language (French and German) articles included where possible from the 1900s to the present day. RESULTS: Necrotising ulcerative gingivitis is a rare disease (prevalence <1%), with an acute, painful and destructive presentation. It is an opportunistic bacterial infection which is predominantly associated with spirochetes. Treatment of NUG must be provided on a case-by-case basis, tailored to what the individual can tolerate and the extent of the infection. CONCLUSION: Although there is low prevalence of NUG, its importance should not be underestimated as one of the most severe responses to the oral biofilm. Risk factors must be investigated and addressed. Treatment should consist of gentle superficial debridement, oral hygiene instruction and prescription of mouthwash and antibiotics in severe cases.

Clinical and Histopathologic Characterization of Canine Chronic Ulcerative Stomatitis.

Canine chronic ulcerative stomatitis, also known as chronic ulcerative paradental stomatitis, is a painful condition of the oral cavity. The purpose of this study was to determine if there are commonalities in clinical and radiographic features among patients, whether the histopathologic evaluation might inform the pathogenesis, and whether the condition appears similar to human oral mucosal diseases. To do this, we prospectively collected clinical, radiographic, and histopathologic data from 20 dogs diagnosed with the disease. Clinical data were based on a clinical disease activity index, oral and periodontal examination parameters, and full-mouth dental radiographs. The histopathological and immunohistochemical data were based on oral mucosal samples obtained from erosive or ulcerated areas. Our findings revealed that canine chronic stomatitis is clinically characterized by painful oral mucosal ulcers of varying size, pattern, appearance, and distribution, most often associated with teeth with early periodontitis. Histologic examination revealed a subepithelial lichenoid band (interface mucositis) where B cells, T cells, and Forkhead-box protein 3 (FoxP3)- and interleukin-17-expressing cells were present. These cells might play a role in the underlying immune response and an immune-mediated pathogenesis is suspected. The clinical and histopathologic features of this chronic inflammatory mucosal disease in dogs resemble those of oral lichen planus in humans.

[Necrotizing ulcerative diseases in military population].

Necrotizing ulcerative diseases were prevalent in military personnel throughout history. Nowadays, its prevalence declined substantially in industrialized countries. Studies among immunocompromised patients suggest it is still a reason for concern among this population. We present two cases diagnosed and treated at our department. It seems that necrotizing ulcerative diseases are still a relevant entity in the Israeli Defense forces therefore it is of great importance to conduct proper diagnosis, treatment and follow up of the patients.

Clinical diagnosis and treatment of necrotizing ulcerative gingivitis in the orthodontic patient: a case report / Diagnóstico clínico y tratamiento de la gingivitis ulcerativa necrotizante en el paciente ortodóntico: reporte de un caso

Abstract: Introduction: about 0.1 percent of the population suffers from necrotizing ulcerative gingivitis, a disease of rapid progression and acute manifestation, which may progress to necrotizing ulcerative periodontitis and eventually to bone sequestration and loss of gingival tissue. Case report: A 21-year-old female patient undergoing orthodontic treatment for six months, diagnosed with necrotizing ulcerative gingivitis due to acute pain in the gingival tissue, spontaneous bleeding, halitosis and abundant plaque. The treatment was conservative and effective, obtaining total remission of the lesion after seven days and three months of postoperative follow-up. Conclusion: Today there are no epidemiological or clinical reports that support the relationship of necrotizing ulcerative gingivitis and orthodontic treatment. Prevention is critical to the success of the treatment, which is why the dentist should recognize the clinical features of necrotizing ulcerative gingivitis to raise awareness of its risks in the orthodontic patient.

Resumen: Introducción: alrededor del 0.1 por ciento de la población padece de gingivitis ulcerativa necrotizante, una enfermedad de progresión rápida y de presentación aguda que puede progresar a periodontitis ulcerativa necrotizante llegando a desarrollarse secuestros óseos y la pérdida de tejido gingival. Reporte del caso: Paciente femenino de 21 años de edad bajo seis meses de tratamiento ortodóntico, quien fue diagnosticada con gingivitis ulcerativa necrosante, debido a dolor agudo en el tejido gingival, sangrado espontáneo, halitosis y abundante placa bacteriana. El tratamiento fue llevado a cabo de manera conservadora y efectiva, obteniendo la remisión total de la lesión al término de siete días y los tres meses de seguimiento postoperatorio. Conclusión: Hoy en día no existen reportes epidemiológicos ni clínicos que sustenten la relación de la gingivitis ulcerativa necrotizante y el tratamiento ortodóntico. La prevención es decisiva para el éxito del tratamiento, es por ello que el odontólogo debe conocer las características clínicas de la gingivitis ulcerativa necrotizante para hacer conciencia en el paciente ortodóntico.

Necrotizing Periodontal Diseases in Children: A Literature Review and Adjustment of Treatment.

Necrotizing ulcerative gingivitis, sometimes observed in young children, may lead to necrotizing stomatitis and noma. Therefore, its interception is a necessity and a challenge for the paediatric practitioners. First, this article aims to propose a systematic review of recent literature on the use of local antiseptic and antibiotic prescription in this particular periodontal condition. Then, a protocol is proposed to have a simple, costless and reproducible treatment on children.

The diagnostic challenges of separating chronic ulcerative stomatitis from oral lichen planus.

OBJECTIVE: To attempt to establish criteria to differentiate between chronic ulcerative stomatitis (CUS) and oral lichen planus (OLP) with hematoxylin and eosin (H&E) staining alone. STUDY DESIGN: Ten confirmed cases of CUS were reviewed from the Stomatology Clinic at the Texas A&M University Baylor College of Dentistry. RESULTS: The original diagnosis on H&E evaluation was OLP, chronic mucositis, or mucositis with lichenoid features, but subsequent direct immunofluorescence (DIF) revealed a positive speckled intranuclear deposition of immunoglobulin G (IgG) in the basal and parabasal layers of the epithelium, confirming a diagnosis of CUS. CONCLUSIONS: No consistent histopathologic features were present that would allow recognition of CUS from H&E analysis alone. DIF remains the gold standard for diagnosis.

Assessment of the calibration of periodontal diagnosis and treatment planning among dental students at three dental schools.

Calibration in diagnosis and treatment planning is difficult to achieve due to variations that exist in clinical interpretation. To determine if dental faculty members are consistent in teaching how to diagnose and treat periodontal disease, variations among dental students can be evaluated. A previous study reported high variability in diagnoses and treatment plans of periodontal cases at Indiana University School of Dentistry. This study aimed to build on that one by extending the research to two additional schools: Marquette University School of Dentistry and West Virginia University School of Dentistry. Diagnosis and treatment planning by 40 third- and fourth-year dental students were assessed at each of the schools. Students were asked to select the diagnosis and treatment plans on a questionnaire pertaining to 11 cases. Their responses were compared using chi-square tests, and multirater kappa statistics were used to assess agreement between classes and between schools. Logistic regression models were used to evaluate the effects of school, class year, prior experience, and GPA/class rank on correct responses. One case had a statistically significant difference in responses between third- and fourth-year dental students. Kappas for school agreement and class agreement were low. The students from Indiana University had higher diagnosis and treatment agreements than the Marquette University students, and the Marquette students fared better than the West Virginia University students. This study can help restructure future periodontal courses for a better understanding of periodontal diagnosis and treatment planning.

The tricho-rhino-phalangeal syndrome: oral manifestations and management.

Tricho-rhino-phalangeal Syndrome (TRPS) is a rare inherited dysplasia affecting hair, nasal structure and fingers. A literature review indicated that since first described, three types of manifestations have been identified. A Table summarising the oral manifestations demonstrates the variety of presentations. A South African male child presented with the syndrome and was found to show premature eruption of permanent teeth, a finding that has not been previously reported. His oro-facial manifestations also included malaligned and unerupted crowded teeth, bulbosity of the nasal tip and an elongated philtrum and evidence of mild intellectual impairment. A protocol has been developed to guide the future management of these cases.

Aggressive and acute periodontal diseases.

Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount.