Effect of local nifedipine administration on rat gingiva.

BACKGROUND: Nifedipine, a calcium channel-blocking agent, has been associated with gingival enlargement in humans. This enlargement has also been successfully established in animal models. Previous investigators have administered nifedipine through a systemic route, most commonly by oral intake. The aim of the present study was to measure the effects of nifedipine administered directly into rat gingival interproximal papillae. METHODS: Twenty-four adult female rats were assigned to three groups. Each animal received a series of three injections, one week apart; each injection was placed directly into the interdental papilla of the maxillary and mandibular central incisors. Group 1 (control) received only saline. Group 2 received a low (10 microg/ml) concentration of nifedipine, while Group 3 received a higher concentration (500 microg/ml). One week after the last series of injections, gingival specimens were harvested from the injection site and prepared for histological and immunocytochemical analyses. RESULTS: Specimens from Group 3 displayed a significantly greater number of ED2-positive cells compared to the other two groups. Specimens from Group 2 showed a significantly higher mean count of positive cells compared to Group 1. Collectively, our data suggest that repeated local injections of 10 microg/ml and 500 microg/ml nifedipine each elicit an inflammatory response in the gingival connective tissue. CONCLUSIONS: Immunocytochemical analysis revealed dose-dependent increases of resident tissue macrophages in rats receiving nifedipine (p<0.005). An increased inflammatory infiltrate also was observed via routine histology. Gross macroscopic changes consistent with gingival enlargement were not observed.

Inflammatory response to dental polishing and prophylaxis materials in rats.

OBJECTIVE: To describe the tissue response to implanted polishing and prophylaxis materials using a rat model system. MATERIAL AND METHODS: Two polishing pastes (diamond polishing paste and aluminum polishing paste), two prophylaxis materials (prophylaxis paste with fluoride and air polishing prophylaxis powder) and negative and positive controls were subcutaneously implanted in rats. Tissue specimens obtained after 2 days, 1, 4, 6 and 8 weeks after implantation were processed for routine hematoxylin and eosin staining and polarized light evaluation. RESULTS: Air polishing prophylaxis powder produced a mild inflammatory response. A more intense inflammation was elicited by diamond polishing paste, and the prophylaxis paste with fluoride elicited an even greater response. The aluminum polishing paste produced the most severe and persistent tissue response, which was of the granulomatous type. CONCLUSIONS: This finding suggests that foreign body reaction should be considered in a gingivitis that does not respond to plaque control or does not represent a mucocutaneous lesion.

Linear IgA Disease of the Gingiva Following Nivolumab Therapy.

Immunotherapy has advanced the treatment of solid organ malignancies. Although generally well tolerated, treatment with immune checkpoint inhibitors can be complicated by immune-related adverse events, some of which are relatively uncommon. We report the first case of gingival linear immunoglobulin A disease related to treatment with an antiprogrammed cell death protein 1 antibody. A 73-year-old male with advanced non-small cell lung cancer achieved a durable response to nivolumab monotherapy. After 1 year of treatment, he developed gingival swelling and pain. Biopsy revealed linear immunoglobulin A disease of the gingiva which was effectively treated with systemic steroids. Ongoing vigilance for immune-mediated toxicity is paramount during and after treatment with immune checkpoint inhibitors.

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.

Multicentric Squamous Odontogenic Tumor: A Case Report and Review of the Literature.

Squamous odontogenic tumor (SOT) is a rare benign epithelial odontogenic neoplasm of the jaws. Both intraosseous and peripheral SOTs have been described in the English language literature. While most intraosseous SOTs occur as solitary lesions, a multicentric variant has also been previously described. Although the radiographic and microscopic features are identical for both solitary and multicentric clinical presentations, there are three significant differences between them. More specifically, multicentric SOT presents at an earlier age (third decade of life), has a slightly higher male to female ratio than the solitary type and has a marked predilection for African-Americans. Here we document the eighth reported case of multicentric SOT, which was diagnosed in a 43-year-old African-American male. In addition, we feature focal sebaceous metaplasia, a heretofore unknown microscopic feature of SOT. Clinical, radiological, and histopathological findings are discussed. The differential diagnosis, biological behavior and management modalities for SOT are also addressed.

Indications and procedures for direct immunofluorescence biopsies of the oral mucosa.

A definitive diagnosis is crucial for management of any oral mucosal disease. Direct immunofluorescence (DIF) is a valuable diagnostic aid for immune-mediated blistering diseases and systemic connective tissue diseases of the skin and the mucosa. This paper gives an overview of the DIF biopsy technique for oral lesions and provides a background for the clinician to optimize the utilization of DIF biopsy. The key characteristic diagnostic findings of DIF of specific mucosal diseases are also discussed.

Oral pemphigoid masquerading as necrotizing ulcerative gingivitis in a child.

BACKGROUND: Cicatricial pemphigoid (benign mucous membrane pemphigoid) is an autoimmune vesiculobullous disease that affects mucosal tissues of adults and rarely presents in children. Only 9 cases in the English literature have reported cicatricial pemphigoid in children, primarily as oral mucosal lesions. This paper presents a case of childhood cicatricial pemphigoid that clinically manifested as necrotizing ulcerative gingivitis (NUG). METHODS: A 9-year-old girl presented with gingival bleeding and discomfort for 2 weeks. NUG was suspected and the patient was treated with antibiotics and an oral hygiene regimen. When the condition did not improve after repeated treatment trials, routine hematoxylin and eosin (H&E) and direct immunofluorescence examinations were performed. RESULTS: Microscopic examination of H&E stained sections showed a non-specific ulceration with chronic inflammation. Direct immunofluorescence studies of peri-lesional tissue showed linear deposition of C3 at the basement membrane zone that was consistent with a diagnosis of cicatricial pemphigoid. CONCLUSION: Cicatricial pemphigoid is an autoimmune ulcerative condition that is rarely seen in children. Immunofluorescence studies are essential to differentiate this condition from other ulcerative oral lesions.

Recurrent recalcitrant gingival hyperplasia and plasminogen deficiency: a case report.

BACKGROUND: Recurrent gingival hyperplasia due to plasminogen deficiency is a rare condition due to fibrin deposition in the connective tissue. Only eight cases have previously been reported in the English literature, and all cases were diagnosed before the age of 35 years. This paper presents an older patient with recurrent gingival hyperplasia due to plasminogen deficiency (hypoplasminogenemia). METHODS: A 59-year-old woman presented with recurrent gingival swelling of 6 years' duration. Multiple biopsies performed at various time periods were histologically reported to be gingival hyperplasia with chronic inflammation. Routine hematoxylin and eosin (H & E) staining and direct immunofluorescence were performed. RESULTS: H & E-stained sections showed subepithelial, eosinophilic, amorphous, acellular deposits. Direct immunofluorescence showed positive staining for fibrin, immunoglobulin (Ig) G, IgA, and IgM. Functional plasminogen and plasminogen activator inhibitor-1 assays were done and found to be deficient. A diagnosis of gingival hyperplasia due to plasminogen deficiency (hypoplasminogenemia) was rendered. CONCLUSIONS: Recurrent gingival hyperplasia due to plasminogen deficiency (hypoplasminogenemia) is a newly recognized and rare condition. H & E staining, direct immunofluorescence, and assessment of functional plasminogen levels are essential to differentiate this condition from other conditions in which subepithelial, eosinophilic, amorphous materials are deposited.

Chronic ulcerative stomatitis: clinical, histopathologic, and immunopathologic findings.

Chronic ulcerative stomatitis (CUS) is a mucocutaneous disease primarily involving mucosal surfaces, but occasionally may involve the skin. Clinically, CUS patients exhibit erosive or ulcerative lesions of the oral mucosa that resemble erosive oral lichen planus. Direct immunofluorescence (DIF) studies of mucosal or skin biopsies reveal a unique pattern of IgG immunoglobulin bound to nuclei of keratinocytes of the basal and lower one third cell layers, the stratified epithelial specific (SES) antinuclear antibody (ANA) pattern. Patient sera also exhibit circulating SES-ANA reactions on indirect immunofluorescence (IIF) using an esophagus substrate. We report the clinical and immunopathologic findings of 3 cases of CUS and demonstrate autoantibody recognition of the CUS antigen on Western blot. An important reason to distinguish CUS from other oral ulcerative conditions is that it may be refractory to standard treatments with topical corticosteroids, and favorable clinical responses may be achieved with hydroxychloroquine pharmacotherapy.

Collagen as an implantable material in medicine and dentistry.

Collagen is a highly versatile material, extensively used in the medical, dental, and pharmacological fields. Collagen is capable of being prepared into cross-linked compacted solids or into lattice-like gels. Resorbable forms of collagen have been used to dress oral wounds, for closure of graft and extraction sites, and to promote healing. Collagen-based membranes also have been used in periodontal and implant therapy as barriers to prevent epithelial migration and allow cells with regenerative capacity to repopulate the defect area. It has been hypothesized that membrane regenerative techniques facilitate the natural biological potential by creating a favorable environment for periodontal and peri-implant regeneration. Due to the enormous potential of collagen-based regenerative barriers, clinicians may benefit from a review of potential applications of implantable collagen and knowledge of collagen preparation and membrane types as well as from as awareness of the functional and degradation properties of those materials.

Erupted complex odontoma: a case report and literature review.

A case involving a 17-year-old girl with a large erupted odontoma associated with a deeply impacted mandibular molar is reported. The molar, which previously had been displaced to the border of the mandible, erupted successfully three years after surgical removal of the odontoma. A review of the literature presents guidelines for treating similar cases.

Definitive and differential diagnosis of desquamative gingivitis through direct immunofluorescence studies.

BACKGROUND: Desquamative gingivitis (DG) is a common clinical manifestation of oral autoimmune vesiculobullous diseases (VBDs). Their polymorphous clinical presentations coupled with similar histologic features make diagnosis indistinguishable among the different VBDs. Direct immunofluorescence (IF) studies are valuable gold-standard diagnostic tests that allow for discrimination among the various VBDs that present with DG. There have been no recent detailed analyses done that have used conventional light microscopy and direct IF in diagnosis to document the clinical associations of DG with various autoimmune oral diseases. The aim of this study is to examine retrospectively a large cohort of patients with DG for associated diseases and to determine the utility of direct IF and conventional light microscopy in establishing a definitive diagnosis. METHODS: During a 14-month period, our laboratory in Buffalo, New York, received 239 consecutive archival cases of gingival biopsy with a clinical diagnosis of DG. These specimens were submitted to establish or rule out a diagnosis of a direct IF-positive VBD. The demographic, clinical, and microscopic findings were tabulated using established inclusion and diagnostic criteria. RESULTS: Approximately half the number (48.1%) of biopsies received for direct IF studies were submitted by periodontists. Slightly more than half of the patients (53%) previously had biopsies submitted for both hematoxylin and eosin (H & E) and direct IF testing. There was a female predilection for all the diseases studied except for pemphigus and linear immunoglobulin A disease. Oral lichen planus was the most common disease presenting as DG, followed by pemphigoid. The clinical diagnosis of lichen planus correlated with the biopsy findings in 80% of the cases and with pemphigoid in 60%. Definitive diagnosis was rendered to ≈80% of the gingival biopsies submitted. Negative cases of direct IF presenting as DG had significant pathology, such as dysplasia and carcinoma, which would have been otherwise missed if H & E studies had not been performed. CONCLUSIONS: This study has the largest cohort of patients with DG suspected of VBD reported in the literature. The patients were predominantly females who had most often been seen by a periodontist. The definitive diagnosis of DG was most accurately achieved when H & E along with two biopsies for direct IF studies were submitted for testing. H & E studies were particularly important for definitive diagnosis of negative cases. Oral lichen planus was the most common disease presenting as DG, which is consistent with recent studies. Systemic connective tissue disorders that present as DG at initial clinical examination require direct IF and serum studies for a conclusive diagnosis. Clinical pathologic correlation, including history, presentation, H & E, and direct IF studies, are essential in establishing a definitive and differential diagnosis for cases presenting with DG.

The nature and frequency of medical emergencies among patients in a dental school setting.

As health care improves and life expectancy increases, dentists and dental students are treating a growing number of elderly and medically compromised patients, increasing the likelihood of a medical emergency during treatment. Previous studies examining emergencies in a dental setting have relied upon self-reports and are therefore subject to biases in reporting. The purpose of this study was to examine data generated from documentation of CODE-5 medical emergency events at the University at Buffalo School of Dental Medicine over an eight-and-a-half-year period. The incidence of emergencies was found to be 164 events per million patient visits, which is lower than reported in previous studies. Most emergencies involved suspected cardiovascular events, syncope, complications related to local anesthesia, and hypoglycemia. Twenty percent of emergencies involved people who were in the building for reasons other than to receive dental care, underscoring the need for an operational CODE-5 system whenever a building is occupied. We suggest strategies to reduce the incidence of medical emergencies and increase ability to manage those that do occur.

Clinical and immunopathologic findings in oral lichen planus pemphigoides.

Lichen planus pemphigoides (LPP) is a rare, acquired, immunobullous disorder of skin that occasionally involves oral mucous membranes. Clinical, histologic, and immunopathologic findings of the oral manifestations of LPP are described. Clinical features are lichenoid striae, erosions, and ulcerations involving gingiva and buccal mucosae. Histopathologic features are similar to those of ora lichen planus. Direct immunofluorescence demonstrates linear deposits of immunoglobulin G and complement component C3 along the basement membrane with fibrillar deposits of fibrin at the epithelial/lamina propria junction. Fluorescence overlay antigen mapping and laser scanning confocal microscopy of the biopsy specimen exhibits colocalization of in situ antibodies with beta4 integrin, a marker of the keratinocyte basal plasma membrane and upper lamina lucida, consistent with the location of the bullous pemphigoid antigens. This case report describes a case of LPP that presented exclusively as an oral condition. Lichen planus pemphigoides should be considered in the clinical differential diagnosis of vesiculoerosive oral mucosal diseases.

Cellular inflammatory response to porcine collagen membranes.

OBJECTIVES: The purpose of this study was to assess local inflammatory changes associated with the implantation of three different porcine collagen membranes having potential use in periodontal regeneration. METHODS: Materials were implanted subcutaneously into prepared sites along the dorsal skin surface of 60 female Wistar rats. Saline and turpentine were used as negative and positive controls, respectively. Animals were killed and biopsies obtained after 3 d, and at 1, 2, 4, 6, and 8 weeks after membrane implantation. A panel of six monoclonal antibodies was used to identify circulating monocytes (ED1), resident tissue macrophages (ED2), lymphoid macrophages (ED3), Ia-antigen expression (OX6), T-lymphocytes (OX19), and B-lymphocytes (OX33). Cells identified by each antibody were subjected to quantitative immunocytochemistry to compare any differences present among groups. Sera obtained 8 weeks after grafting were used in immunoblotting assays to detect the presence of systemic antiporcine antibodies. RESULTS: We found that the mononuclear cell subsets associated with implantation of porcine collagen membranes were similar to those obtained with saline administration. On the other hand, the use of turpentine resulted in an inflammatory infiltrate characterized by significantly higher numbers of all six monoclonal cell subsets at all time periods evaluated, compared to either saline or any of the membranes (P < 0.001). CONCLUSIONS: The collagen membranes do not appear to be associated with a significant local inflammatory response, nor a systemic immune response, and thus appear to be well tolerated, rendering them useful in periodontal regeneration.

Collagen: an overview.

Collagen is a versatile material with biological properties that make it useful for the fabrication of implantable devices in medicine and dentistry. In this article we review collagen biosynthesis, structure, and types, as well as the properties that make it compatible with human tissues.