Indicators of antioxidant protection of blood in necrotizing ulcerative gingivitis in experimental animals.

This article highlights the results of a study of blood parameters in animals with simulated necrotizing ulcerative gingivitis and compares them, under the same conditions, with animals that received local treatment with a developed complex of antioxidant drugs. Following the work tasks, the nature of changes in the state of the antioxidant - prooxidant system and their influence on quantitative and functional indicators of markers of inflammatory intensity was analyzed and investigated during the pathological process in the background and without treatment with a developed complex. This work shows the changes of malonic dialdehyde concentration as an indicator of lipid peroxidation intensity in experimental animals, the level of catalase activity in the blood of animals, and antioxidant-prooxidant balance in the dynamics of necrotizing ulcerative gingivitis.

Estomatitis Urémica como Complicación Oral de Insuficiencia Renal Crónica: Reporte de Caso y Revisión de la Literatura / Uremic Stomatitis as an Oral Complication of Chronic Renal Failure: Case Report and Literature Review

RESUMEN: La Estomatitis Urémica es una lesión oral poco frecuente que se presenta generalmente en pacientes con insuficiencia renal crónica avanzada o no tratada. A continuación, se reporta un caso clínico de un paciente masculino de 22 años de edad que acude a un servicio de urgencia con la presencia de placas blanquecinas indoloras en piso de boca, cara interna de mejilla, y lengua. Las probables causas, presentaciones clínicas, y manejo odontológico son discutidos.

ABSTRACT: Uremic stomatitis is a rare oral lesion that usually occurs in patients with advanced or untreated chronic renal failure. Here we report a case of a 22-year-old male patient who comes to an emergency department with the presence of painless whitish plaques on the floor of the mouth, internal cheek face, and tongue. Probable causes, clinical presentations, and dental management are discussed.

Oral manifestations of HIV infection and their correlation with CD4 count.

Human Immunodeficiency Virus (HIV)-related oral lesions can be used as markers of the immune status. The present cross-sectional study was conducted to identify the oral manifestations in HIV-infected individuals and their association with reduced Cluster of Differentiation 4 (CD4) count. The study population included known HIV-positive patients. A detailed case history of 399 HIV-positive patients was obtained and general examination was carried out. Diagnosis of oral lesions was done based on presumptive criteria of EEC Clearinghouse, 1993. The CD4 count was determined in 369 patients and correlated with oral manifestations. The prevalence of oral lesions was found to be 76.70% (n = 306). Oral candidiasis (157 (39.3%)) was the most common oral lesion associated with HIV infection. Amongst various forms of oral candidiasis, erythematous candidiasis (122 (39.3%)) outnumbered the other forms. The mean CD4 count of patients with oral lesions (207 cells/mm(3)) was less than in patients without oral lesions (291 cells/mm(3)) (P = 0.002). Oral candidiasis was found to be significantly correlated to a reduced CD4 cell count below 200 cells/mm(3) (P = 0.000; Odds ratio = 3.1; 95% Confidence interval 1.9-4.9) with good sensitivity, best specificity and positive predictive value. Oral manifestations may be used as an alternative to CD4 count at field-based settings to diagnose the immune compromised status of HIV-infected individuals.

Chronic ulcerative stomatitis: evidence of autoimmune pathogenesis.

OBJECTIVES: Chronic ulcerative stomatitis is a condition characterized by chronic, painful oral ulcers, whose pathogenesis is unknown. Patients demonstrate specific IgG autoantibodies against ΔNp63α, an epithelial nuclear transcription factor. The aim of this study was to investigate the role of patient autoantibodies in the disease pathogenesis. METHODS: Three-dimensional in vitro tissues consisting of a fully differentiated, multilayer epithelium that mimics its in vivo counterpart were incubated with serum from patients with chronic ulcerative stomatitis. RESULTS: Our results show a subepithelial detachment of the epithelium at the basement membrane interface, mimicking the oral ulcerations that are seen clinically. Expression of basement membrane proteins Type IV collagen and laminin-5 was unaltered, whereas the expression of α6ß4 integrins, hemidesmosome components that attach basal keratinocytes to the basement membrane, was reduced, as determined by immunohistochemistry. CONCLUSION: These results give evidence that patient autoantibodies are pathogenic; and support an autoimmune pathogenesis in chronic ulcerative stomatitis.

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.

Patients with oral erosive and cutaneous lichen planus may have antibodies directed against the chronic ulcerative stomatitis protein antigen of 70-kDa.

OBJECTIVE: The aim of this study is to verify whether stratified epithelium-specific antinuclear antibodies are present in the sera of patients with erosive oral lichen planus and cutaneous lichen planus. METHODS: We studied the pre-immune and immune serum of a rabbit immunized with a peptide corresponding to the N-terminus of the 70-kDa antigen chronic ulcerative stomatitis protein; sera from two patients, one with oral erosive lichen planus and one with cutaneous lichen planus who presented stratified epithelium-specific antinuclear antibodies at high titer; and a third serum from a patient with cutaneous lichen planus without stratified epithelium-specific antinuclear antibodies. RESULTS: We demonstrated that the protein bands recognized by the serum of the rabbit immunized with an epitope of chronic ulcerative stomatitis protein co-migrated by SDS-PAGE with the protein bands recognized by the serum of a patient affected by oral erosive lichen planus and by the serum of a patient with cutaneous lichen planus, both containing antibodies directed against a 70-kDa antigen. CONCLUSIONS: Our results confirm that antibodies specifically directed against the chronic ulcerative stomatitis protein are not a distinctive marker of chronic ulcerative stomatitis, but may also be detected in oral erosive and cutaneous lichen planus.

Autoimmunity to deltaNp63alpha in chronic ulcerative stomatitis.

Chronic ulcerative stomatitis (CUS) is a recently described mucocutaneous condition in which patients experience chronic, painful, ulcerative lesions of the oral mucosa. CUS is diagnosed by immunofluorescence studies that demonstrate antinuclear antibodies. These autoantibodies are specific for a protein, deltaNp63alpha, which is normally expressed in basal cell nuclei of stratified squamous epithelia. The purpose of this study was to characterize the autoimmune response in CUS. Protein antigens were produced by in vitro transcription/translation of polymerase chain-reaction (PCR)-amplified cDNAs. We used immunoblotting and immunoprecipitation experiments with serum from CUS patients to examine the (1) antibody isotype, (2) immunogenic functional domains of the deltaNp63alpha antigen, and (3) cross-reactivity with homologous p53, p73, and p63 proteins. Results demonstrate CUS patient antibodies to deltaNp63alpha, and 52% of cases have circulating IgA isotype antibodies. The N-terminal and DNA-binding domains are the immunodominant regions, and antibody cross-reactivity with p53, p63, and p73 isoforms is limited.

Ulcerative uremic stomatitis associated with untreated chronic renal failure: report of a case and review of the literature.

Uremic stomatitis represents a relatively uncommon intraoral complication seen, mostly, in cases of end-stage renal disease or undiagnosed/untreated chronic renal failure. Its incidence has decreased due to the advent of renal dialysis. Clinically uremic stomatitis is characterized by the presence of painful plaques and crusts that are usually distributed on the buccal mucosa, dorsal or ventral surface of the tongue, gingiva, lips, and floor of the mouth. Treatment consists of improvement of urea blood concentration and the underlying renal failure, supported by increased oral hygiene with antiseptic mouthwashes and antimicrobial/antifungal agents if necessary. Although uremic stomatitis occurs in patients with end-stage renal disease, we report a case of a patient who exhibited an ulcerative form of uremic stomatitis related to the sudden relapse of uremia, although not in an advanced stage of her renal disease. A description of the clinical and microscopic appearance is given along with our hypothesis for the pathogenesis of the disease.

Inflammatory cytokine profile and circulating cortisol levels in malnourished children with necrotizing ulcerative gingivitis.

Necrotizing ulcerative gingivitis (NUG), a periodontal disease traditionally associated with stressful lifestyles in young adults in developed countries, is very prevalent in socioeconomically deprived Nigerian children. Random incident cases (153) of NUG, along with their neighborhood village counterparts of comparable age and without NUG, as control, were recruited for this study. Anthropometric evaluation revealed widespread malnutrition and poor health in both groups of children, with more severe stunting in NUG cases. The poor nutritional status of the village children, with and without NUG, was also confirmed by markedly reduced levels of circulating micronutrients. Compared with the neighborhood children, NUG victims showed significant (p < 0.05 or < 0.001) increases in serum levels of interleukin (IL)-8 (+ 233%), IL-18 (+ 30%), IL-6 (+ 190%), IL-1beta (+ 341%), IL-10 (+ 186%), with a small decrease in interferon (IFN)-gamma (-19%) and nonsignificant increases in soluble tumor necrosis factor (TNF) receptors (sTNFR-p55, p75). Associated with NUG was a significant, 38% (p < 0.05) increase in plasma cortisol above the already high levels observed in the neighborhood village children, as well as some micronutrient deficiencies. The findings suggest that NUG is associated with dysregulated cytokine production, with a complex interplay of elevated levels of pro- and anti-inflammatory mediators. Such changes may serve as the common link between the seemingly unrelated risk conditions (e.g. stressful life styles, smoking, microbial infections, diabetes, malnutrition, alcoholism) traditionally implicated in the genesis of NUG, and all known to promote an increase in the blood level of cortisol, as well as a Th(1) to Th(2) cytokine shift.

Characterization of an autoantigen associated with chronic ulcerative stomatitis: the CUSP autoantigen is a member of the p53 family.

A unique clinical syndrome has been described in which patients have chronic oral ulceration and autoantibodies to nuclei of stratified squamous epithelium. We have characterized the autoantibodies from patients sera and found that the major autoantigen is a 70 kDa epithelial nuclear protein. Sequencing of the cDNA for this protein, chronic ulcerative stomatitis protein, revealed it to be homologous to the p53 tumor suppressor and to the p73 putative tumor suppressor, and to be a splicing variant of the KET gene. The p53-like genes, p73 and the several KET splicing variants, are recently described genes of uncertain biologic and pathologic significance. This study provides the first clear association of a p53-like protein with a disease process.

Necrotizing ulcerative periodontitis associated with severe congenital immunodeficiency in a prepubescent subject: clinical findings and response to intravenous immunoglobulin treatment.

Common variable immunodeficiency (CVID) is a rare multifactorial congenital disease of genetic origin caused by an impairment in the secretion of specific immunoglobulins. It manifests systemically through recurrent respiratory infections, gastrointestinal disorders and autoimmune diseases. Oral manifestations may include gingivitis and lichenoid lesions with Wickham's striae. The treatment for CVID is supported by using intravenous infusion of immunoglobulins (IVIG) that allows for control of the disease and avoidance of recurrent opportunistic infections. This report presents a case of necrotizing ulcerative periodontitis (NUP) in a young patient with CVID, and correlates his periodontal status with systemic conditions before and after IVIG administration during 1 year of evaluation.

Antibodies to Treponema pallidum in serum from subjects with periodontitis: relationship to pathogen-related oral spirochetes.

Pathogen-related oral spirochetes were identified in dental plaque using monoclonal antibodies to putative Treponema pallidum-specific proteins, and serum from subjects with necrotizing ulcerative gingivitis contained immunoglobulin G to molecules thought to be restricted to T. pallidum. The purpose of this study was to determine whether subjects with periodontitis were more likely to have serum antibodies to T. pallidum if pathogen-related oral spirochetes were present. Pathogen-related oral spirochetes were detected in subgingival plaque from 27 of 40 subjects, and 33 subjects had serum antibodies that bound T. pallidum proteins in immunoblots. Subjects with pathogen-related oral spirochetes were no more likely to have IgA, IgG or IgM to 15-, 37- or 47-kDa proteins than were subjects without pathogen-related oral spirochetes. In contrast to subjects with necrotizing ulcerative gingivitis, subjects with periodontitis had no detectable antibodies to 37- or 12-kDa proteins. Further research is needed to identify the stimulus for antibodies that cross-react with T. pallidum proteins.

Correlation of oral disease with the Walter Reed staging scheme for HIV-1-seropositive patients.

This study correlates the prevalent oral disease findings in 390 patients seropositive for human immunodeficiency virus type 1 (HIV-1) with their level of staging (Walter Reed) and depletion of peripheral helper T lymphocytes (CD4+). Chronic lymphadenopathy of the head and neck was a common finding (59.2%) that occurred early in staging progression and did not correlate with depression of helper T-cell levels. Of the three prevalent oral disease findings (oral hairy leukoplakia (OHL), candidiasis, necrotizing ulcerative gingivitis [NUG]) only OHL and NUG were significantly correlated with helper T-cell depletion. The occurrence of visually detectable OHL and NUG corresponds to depletion of peripheral helper T-lymphocyte values in a range of 157 to 299 cells/mm3. This range may represent a more accurate value for biologically significant lymphocyte depletion than the Walter Reed value of 400 cells/mm3. The presence of OHL showed a weak statistical correlation with staging progression, indicating deteriorating immunoregulation. No cases of Kaposi's sarcoma or other HIV-1-associated oral diseases were observed in the sample population, regardless of the patient's staging category or peripheral helper T-lymphocyte count.

A case-control study of plasma ascorbate and acute necrotizing ulcerative gingivitis.

Data from animal studies and from studies of patients with acute necrotizing ulcerative gingivitis (ANUG) have provided suggestive evidence for an association between ascorbate deficiency and disease risk. Further, there is biological plausibility for such an association, due to the role of ascorbate in collagen synthesis and leukocyte function. A case-control study of plasma ascorbate and ANUG was performed on 60 patients with a history of ANUG infection and 60 age-race-sex-matched controls. No cases had had active lesions for at least two months prior to their vitamin assay to avoid any potential reduction of dietary intake of ascorbic acid due to the presence of painful mouth lesions. According to results obtained by use of a modification of the 2,4-dinitrophenylhydrazine method for determination of total plasma ascorbate, the mean and standard error of the mean of plasma ascorbate for all ANUG cases was 0.07 +/- 0.006 mmol/L; the mean for all controls was 0.10 +/- 0.006 mmol/L. Paired differences in plasma ascorbic acid concentrations between cases and controls were significantly different from zero (p less than 0.001). The unadjusted relative risk (RR) of ANUG as obtained by conditional logistic regression for subjects whose plasma ascorbic acid concentration was at or below the median value for controls, relative to subjects with higher values, was 7.3 (90% confidence interval, 3.0 - 17.4; one-sided p value less than 0.001). Patients with a history of ANUG ingested a daily average of 1.2 +/- 0.2 servings of dietary ascorbic acid, as compared with a daily average of 1.9 +/- 0.2 servings for healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukocyte function in the etiology of acute necrotizing ulcerative gingivitis.

Patients with the diagnosis of acute necrotizing ulcerative gingivitis (ANUG) and their controls, matched for age, sex, race and general plaque accumulation, donated blood for differential white blood cell counts and for assay of several leukocyte functions. The leukocyte function assays included polymorphonuclear leukocyte (PMN) responsiveness to chemotaxis and phagocytosis, and lymphocyte responsiveness to stimulation by nonspecific mitogens. The differential leukocyte counts were within the normal range for all subjects tested, and there was no difference between ANUG patients and controls. The ANUG patients did, however, display significantly depressed PMN responsiveness in both chemotaxis and phagocytosis, compared to the controls. There was also reduced DNA synthesis by ANUG patients' lymphocytes upon stimulation by a nonspecific mitogen (Con A). The data presented in this report suggest that depression of some host defense mechanisms, particularly PMN chemotaxis and phagocytosis, may be important in the pathogenesis of ANUG.

Association between ABO blood groups, HL-A antigens and periodontal diseases in young adults: a follow-up study.

Two hundred and thirty-eight Caucasians were studied for ABO blood typing and for HL-A antigens. The subjects were divided into normal, necrotizing ulcerative gingivitis, chronic gingivitis, periodontosis and periodontitis groups. Results showed the chronic gingivitis group was significantly different in ABO grouping than the control group with the gingivitis subjects having a larger percentage of AB types and a smaller percentage of O types. The periodontosis group showed a trend toward more A and B blood groups and a smaller percentage of O groups than the controls. Compared to the normal group there was a significant reduction in HL-A2 antigen frequency in the periodontitis groups and a trend in reduced frequency in the periodontosis group.

Typing Herpesvirus hominis antibodies and isolates by inhibition of the indirect hemagglutination reaction.

Inhibition of the indirect hemagglutination reaction (IHA inhibition) was compared to several other methods for type-specific identification of Herpesvirus hominis (HVH) antibodies and isolates. The method appears to have the greatest value for typing antibodies for HVH type 1 and HVH type 2 in human sera; identification of antibody type was relatively simple and results were definitive. The IHA-inhibition test permitted serological diagnosis of HVH type 2 infection in three young adults with meningoencephalitis, thus extending the mounting evidence that nervous system involvement with this virus type is not limited to neonatal infections. II/I indexes of neutralizing or IHA antibody gave an accurate indication of the presence of HVH type 2 antibody in those sera containing type 2 antibody by IHA inhibition, but they indicated the presence of HVH type 2 antibody in one-half or more of the sera shown to contain only HVH type 1 antibody by IHA inhibition. For typing HVH isolates, the IHA-inhibition test gave results identical to those obtained by direct fluorescent-antibody staining using cross-absorbed conjugates, but the IHA-inhibition test was much more cumbersome and time-consuming to perform than was direct fluorescent-antibody staining. A microneutralization technique for virus typing also gave results identical to those obtained with direct fluorescent-antibody staining and IHA inhibition. However, typing HVH isolates by plaque size or the differential effect of incubation temperature was found to be less definitive and accurate.