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.

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 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.

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.

[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.

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.

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.

Acute periodontal lesions.

This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute disease is under control, definitive treatment should be provided, including appropriate therapy for the pre-existing gingivitis or periodontitis. Among other acute conditions affecting the periodontal tissues, but not caused by the microorganisms present in oral biofilms, infectious diseases, mucocutaneous diseases and traumatic or allergic lesions can be listed. In most cases, the gingival involvement is not severe; however, these conditions are common and may prompt an emergency dental visit. These conditions may have the appearance of an erythematous lesion, which is sometimes erosive. Erosive lesions may be the direct result of trauma or a consequence of the breaking of vesicles and bullae. A proper differential diagnosis is important for adequate management of the case.

Oral medicine case book 65: Necrotising stomatitis.

Necrotising stomatitis is a fulminating anaerobic polybacterial infection affecting predominantly the oral mucosa of debilitated malnourished children or immunosuppressed HIV-seropositive subjects. It starts as necrotising gingivitis which progresses to necrotising periodontitis and subsequently to necrotising stomatitis. In order to prevent the progression of necrotising stomatitis to noma (cancrum oris), affected patients should be vigorously treated and may require admission to hospital. Healthcare personnel should therefore be familiar with the signs and symptoms of necrotising gingivitis/necrotising periodontitis, of their potential sequelae and of the need for immediate therapeutic intervention.

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.

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.

Severe presentation of necrotizing ulcerative periodontitis in a Nigerian HIV-positive patient: a case report.

OBJECTIVE: To report a case of severe necrotizing ulcerative periodontitis (NUP) with a rarely associated sequestrum formation in a Nigerian HIV-positive patient. CLINICAL PRESENTATION AND INTERVENTION: A 47-year-old HIV-positive male patient with no history of previous dental visits presented with a severe toothache in his lower jaw of 4 weeks' duration, which had affected his ability to chew properly. Clinical examination revealed marked gingival inflammation, moderate gingival recession and mobility of some of his lower anterior teeth: 31, 32, and 33. There was also a sequestrum present associated with the affected teeth. His CD4 cell count was 226 cells/mm(3). His viral load was very high (360,082 copies/ml). The intervention included thorough debridement of the necrotic lesion and sequestrectomy. The patient responded well to treatment after 1 week of follow-up. Unfortunately, the CD4 count was not assessed further because the patient was lost to follow-up. CONCLUSION: This case showed that a high CD4 cell count does not necessarily prevent the occurrence of NUP in HIV-positive patients. Intervention might have enhanced a rapid positive response to the treatment within a short time.

Necrotizing ulcerative gingivitis: a discussion of four dissimilar presentations.

BACKGROUND: Necrotizing ulcerative gingivitis (NUG) is a periodontal disease characterized by pain, bleeding, and necrosis of interdental papillae. This series details treatment of four cases, followed by a discussion of the disease. CASE DESCRIPTION: Four patients presented to four practitioners for treatment of severe gingival pain, each eventually being diagnosed with NUG. All patients in this series were successfully treated using accepted protocols, and though each was different with regard to presenting signs and symptoms, all responded similarly to treatment. Similar to the patients described in this series, NUG cases in general can present with varying degrees of involvement from barely-noticeable to starkly severe. CLINICAL IMPLICATIONS: The most severe cases of NUG are often more destructive in appearance than those most commonly seen in textbooks, while in the mildest cases the appearance can almost be mistaken for health.

ELISA test for p63 antibodies in chronic ulcerative stomatitis.

OBJECTIVE: To develop a novel test for chronic ulcerative stomatitis (CUS), a chronic immunologically mediated condition that produces oral ulcerations. Current diagnostic methods require expensive and technically demanding in situ immunofluorescence (IF) studies. DESIGN: An Enzyme-Linked ImmunoSorbent Assay (ELISA) was prepared and tested with serum samples from patients with CUS and negative controls. MATERIALS AND METHODS: The N-terminal portion of the CUS autoantigen, DeltaNp63alpha, was produced as a purified recombinant protein and used to coat ELISA plates. Sera from 25 patients with CUS and 16 negative controls were analyzed for reactive antibodies. The optimal cut-offs for positive and negative samples were determined. MAIN OUTCOME MEASURES: The optimal cut-off of 0.236 resulted in a sensitivity and specificity of the ELISA of 0.80 and 0.75, respectively (exact 95% confidence intervals, P-value of <0.001). RESULTS: The ELISA developed in this study provides a novel and reliable diagnostic assessment to distinguish CUS from other oral ulcerative diseases. CONCLUSIONS: Immunoassay will allow the true incidence and prevalence of CUS to be determined in future studies. When combined with clinical correlations, the ELISA results will facilitate the evaluation of the prognostic utility of antibody titers and allow correlation with treatment responses in individual CUS cases.

Borrelia tonsillitis: common symptoms but uncommon organism.

We present a severe case of acute tonsillitis caused by Borrelia vincenti. B. vincenti does not only cause Plaut-Vincent's angina, but also a more localised infection of the tonsil.

[Differential diagnosis of unilateral necrotic tonsillitis]. / Differenzialdiagnostik der nekrotisierenden Tonsillitis.

BACKGROUND: The best known clinical picture of a one-sided necrotisising, infectious tonsillitis is the by Plaut and Vincent (1894) described angina Plaut-Vincent. In addition to this fusospirochetosis it is in case of necrotisising inflammations in the oropharynx differential-diagnostically important to consider also the anaerobic type Prevotella, especially Prevotella disiens as a potential trigger . MATERIAL AND METHODS: Because the clinical course forms of a necrotisising oropharyngeal inflammations can be very different and complicate so a suitable diagnosis, it is very important to get a complete and perfect cause proof. For getting this proof a correct test production, transport and cultivation are of extreme importance . RESULTS: The type Prevotella consists of different species gram-negative, obligate anaerobic strains. They are regarded as a cause of suppurating inflammations and abscesses of the genital tract and are components of the aerobic anaerobic mixed flora in case of gingival infections. The sole proof in the microbiological culture as a smear test result of a one-sided necrotisising tonsillitis has to be seen as a first description by reason of missing literature . IMPLICATION: As triggers for one-sided necrotisising tonsillitis are considered different causes. Next a carcinoma of the tonsil, Lues, Angina Plaut-Vincent have to be excluded. An infection with Prevotella disiens is an extremely rare variation in contrast. However, the transmission is possible by insufficient hygiene, lack phenomena and sexual intercourse and to consider therefore as an exclusion diagnosis.

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.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

An atypical form of necrotizing periodontitis.

BACKGROUND: Necrotizing ulcerative gingivitis/periodontitis are considered necrotizing periodontal diseases. This case report presents an atypical form of necrotizing periodontitis, which does not fit into this classification. METHODS: A 12-year-old child was referred to our clinic for gingival inflammation, extensive alveolar bone loss, and tooth mobility. Clinical and microbiologic examinations were carried out, and radiographs were taken. Clinical examination revealed soft and hard tissue destruction up to the mucogingival junction at the right maxillary premolar and mandibular incisors. Unusual infections or abnormalities in systemic functions were not detected through clinical and laboratory evaluations made at the Pediatrics Department, Istanbul University. Although an intensive established treatment protocol for necrotizing periodontitis was completed, management of long-standing health conditions could not be achieved because of recurrence of the disease, which caused us to repeat this treatment protocol at short intervals. RESULTS: Investigation led to a diagnosis of an atypical form of necrotizing periodontitis because the disease had a recurrent acute phase even under a standard treatment protocol. CONCLUSIONS: Our patient exhibits an unusual, necrotizing form of periodontal disease. The reason for the rapid rate of periodontal disease progression remains unclear.