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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.

Periodontal diseases are a group of infectious diseases that mainly include gingivitis and periodontitis. Gingivitis is the most prevalent form of periodontal disease in subjects of all ages, including children and adolescents. Less frequent types of periodontal disease include aggressive periodontitis, acute necrotizing ulcerative gingivitis and various diseases of herpesviral and fungal origin. This review aimed to retrieve relevant information from Latin America on the prevalence of periodontal diseases among children and adolescents of the region. Gingivitis was detected in 35% of young Latin American subjects and showed the highest frequencies in Colombia (77%) and Bolivia (73%) and the lowest frequency in Mexico (23%). The frequency of gingivitis in subjects from other Latin American countries was between 31% and 56%. Periodontitis may affect

Noma (cancrum oris) is a destructive necrotising disease affecting orofacial tissues predominantly of malnourished young children. It is characterised by a rapid acute onset which usually starts in the mouth, spreads intra-orally destroying soft tissue and bone and progresses to perforate the facial skin, causing disfigurement. Polybacterial anaerobic infection is critical too, but is not alone sufficient for the initiation of noma. Cofactors, first and foremost malnutrition, but also systemic viral and bacterial infections are crucial to the development of noma. A patient with necrotising stomatitis or noma must be admitted to hospital for antibiotic treatment, fluid and electrolytes as well as nutritional supplementation and general supportive treatment. The epidemiology of noma in the South African population is unknown, and the clinicopathological features are poorly characterised. Although worldwide there is no evidence that HIV infection is a strong risk factor for noma, HIV infection may play a substantial role in the pathogenesis of noma in South Africa.

Objective The primary objective of this study was to determine the prevalence of oral lesions of autoimmune etiology (OLAIE) in a cohort of patients with primary Sjogren's syndrome (pSS). Materials and methods A multi-center retrospective cohort study was conducted at the oral medicine practices of Carolinas Medical Center (CMC), Baylor College of Dentistry (BCD), and the University of Florida (UF). Each site performed a chart review of patients with well-characterized pSS. Clinical variables such as OLAIE, traumatic lesions, and medical conditions were compiled at each site. The association between clinical variables and the presence of OLAIE was then assessed for significance. Results We evaluated 155 patients diagnosed with pSS. Nineteen patients with pSS (12.3%) had an OLAIE. CMC reported 11 (21.2%) patients with OLAIE, while BCD and UF reported 4 (7.3%) and 4 (8.3%), respectively. Eleven of the 19 (58%) patients with OLAIE had lichen planus, 6 (32%) had aphthous stomatitis, 1 (5%) had chronic ulcerative stomatitis, and 1 (5%) had lesions of systemic connective tissue disease by immunofluorescence. Conclusion The results of our analysis suggest that patients with pSS have a 12% prevalence of OLAIE with a wide range (7.3–21.2%) found between practices. This difference is likely related to the different screening protocols for oral dryness between sites.

Oral Diseases (2010) 16, 151–155 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, ΔNp63α, 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

The aim of this study was to assess and quantify the random effects resulting from clustering in the following individual-level periodontal outcomes: presence of clinical attachment loss of > or = 1 mm (CAL1), presence of clinical attachment loss of > or = 3 mm (CAL3), and presence of necrotizing ulcerative gingivitis (NUG); or in the following class-level periodontal outcomes: number of students with CAL1, number of students with CAL3, and number of students with NUG. Mixed-effects logistic regression analysis was used to model these outcomes among 9,162 adolescents in 310 classes in 98 schools spread over 20 communes in the Province of Santiago, Chile, who had been examined for clinical attachment level and NUG, and had completed questionnaires on oral health-related behaviors. The results of all six analyses demonstrated statistically significant random effects, which in all analyses were particularly related to the schools, whereas the class effects were smaller and the commune random effects were almost negligible. The random effects were quantified using the median odds ratio (MOR), and the class-level MOR ranged between 1.05 and 1.51, whereas the school-level MOR values ranged from 2.07 to 2.39. The results of the study demonstrate the potential of the application of multilevel modeling to periodontal epidemiologic data, over and beyond the conventional use of the technique to account for the intrinsic sites-teeth-subject hierarchy in periodontal data.

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.

AIM: The aim of this experiment was to investigate the association between cannabis use and destructive periodontal disease among adolescents. MATERIAL AND METHODS: Data from a population screening examination carried out among Chilean high school students from the Province of Santiago were used to determine whether there was an association between the use of cannabis and signs of periodontal diseases as defined by (1) the presence of necrotizing ulcerative gingival (NUG) lesions or (2) the presence of clinical attachment loss (CAL) > or =3 mm. The cannabis exposures variables considered were "Ever use of cannabis" (yes/no) and "Regular use of cannabis" (yes/no). The associations were investigated using multiple logistic regression analyses adjusted for age, gender, paternal income, paternal education, frequency of tooth-brushing and time since last dental visit. RESULTS: Multiple logistic regression analyses showed that "Ever use of cannabis" was significantly negatively associated with the presence of NUG lesions (OR=0.47 [0.2;0.9]) among non-smokers only. No significant associations were observed between the presence of CAL > or =3 mm and cannabis use in either of the smoking groups. CONCLUSIONS: There was no evidence to suggest that the use of cannabis is positively associated with periodontal diseases in this adolescent population.

Chronic ulcerative stomatitis (CUS) is a recently described condition with specific immunopathologic findings. Demographics indicate that white women in their late middle age are more susceptible to this condition. The clinical history of CUS patients is of painful, exacerbating and remitting oral erosions, and ulcerations. The histologic features are non-specific, with a chronic inflammatory infiltrate, often appearing similar to oral lichen planus (OLP). Diagnosis of CUS requires surgical biopsy with immunofluorescence microscopic examination. Accurate diagnosis is important because the usual treatment option for immunologically mediated diseases, glucocorticoids, is often not effective in treating CUS. However, hydroxychloroquine pharmacotherapy is beneficial in many cases. The lack of awareness of the condition among clinicians and the technical challenges in specimen processing make diagnosis of CUS a challenge, and hence the true prevalence is unknown. Immunofluorescence studies show circulating and tissue-bound autoantibodies to a protein, DeltaNp63alpha, which is a normal component of stratified epithelia. It is unknown if the antibodies are pathogenic, thus the etiology of CUS is also unknown. Studies are needed to elucidate the pathogenesis of CUS, optimize clinical management, and clarify its relationship to OLP and neoplasia.

The study reported in this paper was carried out in the Northwestern and Southwestern regions of Nigeria, between October 1996 and April 1998. The study examined the possible contributory role of living conditions in the development of acute necrotizing gingivitis (ANG) or noma from oral lesions. Questionnaire data obtained from 42 fresh noma cases seen in the Northwest and four fresh cases seen in the Southwest were examined. In addition 46 cases of advanced ANG from the Southwest were included. The main focus was to compare some of the environmental living conditions of cases with advanced ANG and those with noma in these regions. All the noma and ANG cases were seen in children aged 2-12 years. The level of good oral hygiene practices and general environmental living conditions were significantly higher in the Southwest than in the Northwest. Data also showed that living in close proximity with livestock was significantly higher in the Northwest than in the Southwest (P < 0.05). The environmental living conditions of children in the Northwest were further compounded by poor sanitary faecal disposal practices as well as minimal access to potable water. The overall data indicated that living in substandard accommodations, exposure to debilitating childhood diseases, living in close proximity to livestock, poor oral hygiene, limited access to potable water and poor sanitary disposal of human and animal faecal waste could have put the children in the Northwest at higher risk for noma than the children in the Southwest. These could have been responsible for the higher prevalence of noma in the Northwest than in the Southwest.

OBJECTIVE: This report evaluates and compares individual oral lesions and combinations of lesions in predicting progression-free survival in a seroprevalent cohort of men and women with HIV infection. DESIGN: This was a prospective study of HIV-infected patients, initially AIDS-free, followed for approximately 30 months. SETTING: Patients were volunteers examined at an academic medical center and at an inner-city hospital in New York. Participants identified themselves as homosexual men or as injection drug users (IDU). OUTCOME MEASURES: The primary outcome being assessed is time from a baseline oral examination until the development of an AIDS-defining condition or death from any cause within 12 months of the last study visit. Correlation is measured by relative risk (RR). RESULTS: While oral lesions were not predictive of progression among subjects with CD4 > or = 200, they were highly predictive of progression among those with CD4 < 200. For subjects with CD4 < 200, the only individual lesion that was significantly associated with progression-free survival was oral candidiasis (RR = 4.12, P = 0.009). Positivity for one or more lesions in a set demonstrated greater prognostic value among those with CD4 < 200, with RR's of 6.03 (P = 0.018) for the set consisting of oral candidiasis, hairy leukoplakia, and necrotizing ulcerative gingivitis (NUG), and 8.77 (P = 0.036) for the set consisting of the above lesions plus linear gingival erythema (LGE). Analysis by cohort suggested that the improvement in correlation was stronger in homosexual men than in IDU, but this question could not be resolved conclusively with these data. CONCLUSIONS: Lesion sets might be better prognosticators of progression-free survival than individual lesions among HIV-infected subjects with CD4 < 200. Prognostic value of the core lesion set (oral candidiasis and hairy leukoplakia) was enhanced by the addition of other lesions (NUG and LGE) not usually included in HIV staging systems. These results suggest that staging systems for HIV might be improved by the inclusion of other, survival-related oral lesions.

Periodontal disease has been found to be significantly more prevalent and more severe in people with Down syndrome. A series of studies have reported a prevalence of between 58% and 96% for persons younger than 35 years of age. This phenomenon cannot simply be attributed to poor oral hygiene. The etiology of periodontal disease in persons with Down syndrome is complex. In recent years, much focus has been placed on the altered immune response resulting from the underlying genetic disorder. This paper presents an overview of contemporary knowledge on periodontal disease in patients with Down syndrome.

Background Our objective was to examine the construct validity of the Oral Mucositis Assessment Scale (OMAS) in children receiving doxorubicin chemotherapy. Methods Children between 6 and 18 years of age with cancer receiving doxorubicin-containing chemotherapy were included. OMAS was measured on days 7, 10, 14, and 17 after chemotherapy. Other measures of mucositis obtained concurrent with OMAS were the World Health Organization (WHO) mucositis scale and pain visual analogue scale (VAS). We also recorded analgesia administration. Results Sixteen children were studied for 45 post-chemotherapy cycles and 156 OMAS assessments were performed. OMAS was moderately correlated with WHO scores (r = 0.56; P = 0.0006) whereas correlation with the pain VAS was fair (r = 0.37; P = 0.002). OMAS also had fair correlation with the number of doses of topical analgesia (r = 0.43; P = 0.001) and with the cumulative dose of opioid analgesia (r = 0.38; P = 0.003). Conclusions The OMAS is valid for use in mucositis clinical trials for children at least 6 years of age. Pediatr Blood Cancer 2007;49:149–153. © 2006 Wiley-Liss, Inc.

Histoplasmosis is a rare but serious fungal infection commonly presenting as mucosal ulceration of the oral cavity. It is increasingly recognized in Australia but the source of infection remains obscure and it is likely to be under-diagnosed. We report a case of chronic mucosal ulceration which failed to fully respond to periodontal therapy. Histology and culture of a gingival biopsy was consistent with histoplasmosis, and the patient responded favourably to treatment with oral itraconazole. Histoplasmosis may present to general dental practitioners as chronic mucosal ulceration and should be considered in the differential diagnosis of such lesions. Diagnosis is best made by culture and histology of biopsy specimens.

Desquamative gingivitis is a clinical term to describe red, painful, glazed and friable gingivae which may be a manifestation of some mucocutaneous conditions such as lichen planus or the vesiculobullous disorders. It is important to be aware of this rare clinical entity so as to distinguish desquamative gingivitis from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental practitioner. This article gives an overview of desquamative gingivitis, its presentation, the possible causes, diagnosis and treatment. Early recognition of these lesions may prevent delayed diagnosis and inappropriate treatment of potentially serious dermatological diseases.

Children and adolescents are subject to several periodontal diseases. Although there is a much lower prevalence of destructive periodontal diseases in children than in adults, children can develop severe forms of periodontitis. In some cases, this destructive disease is a manifestation of a known underlying systemic disease. In other young patients, the underlying cause for increased susceptibility and early onset of disease is unknown. These diseases are often familial, suggesting a genetic predisposition for aggressive disease. Current modalities for managing periodontal diseases of children and adolescents may include antibiotic therapy in combination with non-surgical and/or surgical therapy. Since early diagnosis ensures the greatest chance for successful treatment, it is important that children receive a periodontal examination as part of their routine dental visits.

Necrotizing ulcerative periodontitis (NUP) is a painful and potentially debilitating affliction that affects about 2% to 6% of HIV-positive subjects. NUP may be caused by specific microorganisms that are presently unknown or by microbial species not usually thought to cause periodontal infections. The purpose of this study was to define the bacterial species associated with NUP in HIV-positive patients.16S rRNA bacterial genes of DNA isolated from subgingival plaque of 8 HIV-positive subjects with NUP were amplified by polymerase chain reaction (PCR) and cloned into Escherichia coli. The sequences of cloned inserts were used to determine species identity or closest relatives by comparison with known sequences. The microbial profiles in subgingival plaque of subjects with NUP, chronic periodontitis, and periodontal health were compared using a battery of over 200 oligonucleotide probes in a PCR-based, reverse-capture, checkerboard DNA-DNA hybridization assay.Sequence analysis of over 400 clones revealed 108 species; 65 were "uncultivable" phylotypes, of which 26 were novel to NUP subjects. Species or phylotypes most commonly detected were Bulleidia extructa, Dialister, Fusobacterium, Selenomonas, Peptostreptococcus, Veillonella, and the phylum TM7. Based on sequence analysis and checkerboard analysis, NUP did not possess the classical periodontal pathogens such as Porphyromonas gingivalis. Otherwise, the microbial profiles of NUP and periodontitis had many similarities. The microbial profiles of subgingival plaque from periodontally healthy subjects were different and less complex in comparison to the profiles of both disease groups.Certain species appear to be associated with health and periodontal diseases. The putative pathogens associated with periodontal disease in HIV-negative subjects are not associated with NUP in HIV-positive subjects.

Every patient's description of the location of pain must be treated with caution. In order to arrive at a diagnosis of pain a logical method should be employed. This consists of the history and clinical examination including pulp tests and radiographs. Where the patient complains of pain on hot or cold, an attempt should be made to reproduce the patient's pain to check on the accuracy of its description and to aid in localisation. Patients frequently refer pain to previously endodontically-treated teeth. These may not be the cause of the problem. In order to facilitate the process of diagnosis the following hypothesis has been advanced. A tooth can only be the source of pain if there are objective signs associated with that tooth. Lack of response to pulp tests constitutes such a sign, provided the tooth has not previously been endodontically treated. If, however, such treatment has taken place, (regardless of whether this was well or poorly executed), a further objective sign other than lack of vitality is required before such a tooth can be implicated as the source of pain. The guidelines suggested are illustrated by means of clinical examples.

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).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 (HE) and direct immunofluorescence examinations were performed.Microscopic examination of HE 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.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.

In patients with no known systemic disease or immune dysfunction, necrotizing periodontitis (NUP) appears to share many of the clinical and etiologic characteristics of necrotizing ulcerative gingivitis (NUG) except that patients with NUP demonstrate loss of clinical attachment and alveolar bone at affected sites. In these patients, NUP may be a sequela of a single or multiple episodes of NUG or may be the result of the occurrence of necrotizing disease at a previously periodontitis-affected site. The existence of immune dysfunction may predispose patients to NUG and NUP, especially when associated with an infection of microorganisms frequently associated with periodontal disease such as Treponema and Selenomonas species, Fuscobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. The role of immune dysfunction is exemplified by the occasionally aggressive nature of necrotic forms of periodontal disease seen in patients with HIV infection or malnutrition, both of which may impact host defenses. Clinical studies of HIV-infected patients have shown that patients with NUP are 20.8 times more likely to have CD4+ cell counts below 200 cells/mm3. However, these same studies have demonstrated that most patients with CD4+ cell counts below 200 cells/mm do not have NUP, suggesting that other factors, in addition to immunocompromisation, are involved. Further studies are needed to define the complex interactions between the microbial, or viral, etiology of necrotic lesions and the immunocompromised host. It is, therefore, recommended that NUG and NUP be classified together under the grouping of necrotizing periodontal diseases based on their clinical characteristics.

Common variable immunodeficieny (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.

Periodontal manifestations of human immunodeficiency virus (HIV) infection were first described in 1987. Initially, the lesions receiving attention were HIV-associated gingivitis (now known as linear gingival erythema [LGE]) and HIV-associated periodontitis (now known as necrotizing ulcerative periodontitis [NUP]). The true prevalence of LGE was difficult to determine due to variable diagnostic criteria. Recently, LGE has been associated with intraoral Candida infection. The prevalence of NUP is low (or = 5%), and this lesion is associated with pronounced immunosuppression. Current focus on the periodontal manifestations of HIV infection centers on rapid progression of chronic adult periodontitis in HIV+ patients. Attempts to identify the pathogenesis of the increased progression of periodontitis have not proven successful. For example, analysis of subgingival plaque for the presence of bacterial pathogens has failed to detect differences between HIV+ and HIV- patients. Recently our laboratory has identified alterations in the host response in the gingival crevice of HIV+ patients. Comparing HIV+ and HIV- injecting drug users (IDU), levels of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF) were slightly elevated at sites with a probing depth of 1 to 3 mm. At deeper sites (or = 4 mm), total IL-1 beta in GCF was significantly greater in HIV+ individuals. Using the lysosomal acid glycohydrolase beta-glucuronidase (beta G) as a measure of the influx of polymorphonuclear leukocytes (PMN) into the gingival crevice, our data indicated a significant correlation of total beta G in GCF and probing depth in the HIV-IDU (r = 76; P = .02). This result was similar to what we have observed in other studies. In contrast, for HIV+ subjects, total beta G was not associated with probing depth (r = .20; NS). These data suggest that HIV+ patients have altered regulation of PMN recruitment into the gingival crevice. We have begun to investigate the conditions under which subgingival Candida may contribute total periodontal lesions in HIV+ individuals. Candida from subgingival sites has been cultured in HIV+ individuals. Subgingival Candida was distinct from Candida isolated from tongue and buccal mucosal surfaces (as indicated by genomic fingerprinting). We hypothesize the absence of adequate priming of PMN by HIV+ patients. This may be due to a reduced Th1 lymphocyte response. The inability of HIV+ individuals to adequately prime PMN may allow Candida to colonize the subgingival environment. In that milieu, it may act directly or in concert with subgingival bacterial pathogens, or as a cofactor (by inducing production of proinflammatory cytokines) to increase the occurrence of periodontal attachment loss.

All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic in a 5-year period were reviewed and compared against other patients attending the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration. 89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis (ANUG) and responded well to conventional treatment for ANUG. The cases were compared with 269 controls in logistic regression. Gingival ulceration was associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly due to a protective effect of co-trimoxazole medication. 5 patients with neutropenia had extensive ulceration without the microflora of ANUG. Histopathology, viral and bacterial culture revealed non-specific changes. The ulcers did not respond to the treatment regimen for ANUG but responded to treatment of their neutropenia. Gingival ulceration is not common in HIV infection. Most cases resemble severe ANUG. It is more frequent in younger people, those with oral candidiasis and without AIDS. Co-trimoxazole may be protective. A minority of cases with ulceration and associated neutropenia resembled the non-specific oral ulceration associated with HIV.

Herpesviruses have been implicated in the pathogenesis of human periodontitis. The present study investigated whether herpesviruses are present in the lesions of acute necrotizing ulcerative gingivitis. Sixty-two Nigerian children, aged 3-14 years, were studied. Twenty-two children had acute necrotizing ulcerative gingivitis and were also malnourished, 20 exhibited no acute necrotizing ulcerative gingivitis but were malnourished and 20 were free of acute necrotizing ulcerative gingivitis and in a good nutritional state. Polymerase chain reaction methods were used to determine the presence of human cytomegalovirus (HCMV), Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), herpes simplex virus (HSV), human herpes virus 6 (HHV-6), human papilloma virus and human immunodeficiency virus type 1 in crevicular fluid specimens collected by paper points. Of the 22 acute necrotizing ulcerative gingivitis patients, 15 (68%) revealed viral infection and 8 (36%) viral coinfection. Thirteen (59%) acute necrotizing ulcerative gingivitis patients demonstrated HCMV, 6 (27%) EBV-1, 5 (23%) HSV and 1 (5%) HHV-6. Only 2 (10%) subjects from each group not affected by acute necrotizing ulcerative gingivitis showed viral presence, and no control subject revealed viral coinfection. These findings suggest that HCMV and possibly other herpesviruses contribute to the onset and/or progression of acute necrotizing ulcerative gingivitis in malnourished Nigerian children.Recent laboratory studies have implicated herpesviruses in the pathogenesis of human periodontitis. This present study examines whether herpesviruses are present in the lesions of acute necrotizing ulcerative gingivitis. A total of 62 Nigerian children, aged 3-14 years were studied: 22 had acute necrotizing ulcerative gingivitis and were also malnourished, 20 showed no acute necrotizing ulcerative gingivitis but were malnourished, and 20 were free of acute necrotizing ulcerative gingivitis and in a good nutritional state. A polymerase chain reaction assay was used to determine the presence of human cytomegalovirus (HCMV), Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), herpes simplex virus (HSV), human herpes virus 6 (HHV-6), human papilloma virus, and HIV-1 in crevicular fluid samples obtained by paper points. Of the 22 patients with acute necrotizing ulcerative gingivitis, 15 (68%) showed viral infection and 8 (36%) showed a viral coinfection. In addition, 13 (59%) of these patients demonstrated HCMV, 6 (27%) EBV-1, 5 (23%) HSV, and 1 (5%) HHV-6. Only 2 (10%) subjects from each group not affected by acute necrotizing ulcerative gingivitis revealed viral presence, and none of the control group demonstrated viral coinfection. The findings suggest that HCMV and possibly other herpesviruses contribute to the onset and/or progression of acute necrotizing ulcerative gingivitis in malnourished children in Nigeria.

A review of periodontal disease as a manifestation of HIV infection suggests a shift in emphasis over the past 5 years. Initially the focus was on newly described forms of periodontal disease (i.e., HIV-associated gingivitis or linear gingival erythema (LGE); HIV-associated periodontitis or necrotizing ulcerative periodontitis (NUP). While the clinical definition of LGE varies from study to study, an association between LGE and Candida infection has been described. Furthermore, the prevalence of NUP is quite low and this disorder is associated with severe immunosuppression. In contrast, the focus today is on the accelerated rate of chronic adult periodontitis occurring in seropositive patients. While the organisms that characterize adult periodontitis in seronegative individuals are present in subgingival plaque from seropositive individuals, reports suggest that atypical pathogens are also present (i.e., Mycoplasma salivarium, Enterobacter cloacae). Recent studies from our laboratory have identified a novel strain of Clostridium isolated from the subgingival plaque of injecting drug users that has pathologic potential. This organism, however, was found in both seropositive and seronegative individuals in this cohort, suggesting an association with lifestyle rather than serostatus. In addition, data has been published examining the local host response in periodontitis in seropositive individuals. Distinctly elevated levels of IgG in gingival crevicular fluid (GCF) have been observed in seropositive patients. Furthermore, data from our laboratory examining inflammatory mediators in GCF (polymorphonuclear leukocyte lysosomal enzyme beta-glucuronidase and the pro-inflammatory cytokine interleukin-1 beta) suggests an altered response in patients with HIV infection. The alteration manifests as the absence of the expected strong correlation between polymorphonuclear leukocyte activity in the gingival crevice and clinical measures of existing periodontal disease, as well as elevated levels of interleukin-1 beta in sites with deeper probing depths. Therefore, it can be concluded that the progression of periodontal disease in the presence of HIV infection is dependent upon the immunologic competency of the host as well as the local inflammatory response to typical and atypical subgingival microorganisms.

Acquired immunodeficiency syndrome (AIDS) was first recognized in 1981 and in 1983 the virus responsible for this syndrome, the human immunodeficiency virus, was first isolated. There has been an increasing understanding of the many aspects related to infection with this virus and this review discusses the historical as well as the more recent findings related to infection with this virus. In particular, the pathogenesis, mode and course of infection are discussed followed by an overview of the general and oral manifestations of infection with this virus.

HIV-1-associated periodontal diseases have been reported in the literature for several years. Criteria for the diagnosis of these diseases have not been universally accepted, although there are numerous papers describing the clinical entity. These case reports provide clinical and radiographic evidence of a type of periodontal disease with bone and soft tissue destruction which differentiates it from “conventional” periodontal diseases found in both HIV-1-infected patients and those not infected by the virus. It is important, from both diagnostic and therapeutic aspects, for clinicians to be able to make this distinction. The appropriate use of clinical and radiographic findings is extremely helpful in the diagnosis, particularly in the case of defining HIV-1 necrotizing ulcerative periodontitis (NUP). Whether the patterns of gingival changes and bone loss described in these case reports are specific to HIV-1-seropos-itive persons or rather represent severe immunosupp ression requires further investigation.

Abstact Background. In 1990 a new disease-associated antinuclear antibody was first recognized as a specific immunologic marker for a chronic form of ulcerative stomatitis (cus). Methods. Another case is reported herein and the subject of chronic ulcerative stomatitis with stratified epithelium-specific antinuclear antibodies (SES-ANA) is reviewed. Intraoral biopsies from this patient were submitted for microscopic examination and direct immunofluorescence. Indirect immunofluorescence studies were also performed. Serial SES-ANA titers were obtained with the patient on maintenance treatment with hydroxychloroquine. A skin biopsy of a recent lichenoid eruption was obtained and skin explants grown in the serum of this patient were studied in tissue culture with reference to SES-ANA binding and complement fixation. Results. Biopsy and serum studies confirmed a diagnosis of cus with SES-ANA in the patient reported. Skin biopsy showed lichen planus. The patient was treated with hydroxychloroquine with a favorable response. Serial SES-ANA titers did not parallel the disease activity. Among the substantive observations made from skin explants cultured in the serum of this patient was widespread fixation of C3 to the nuclei of basal cells. Conclusions. The case described herein extends the findings in cus to include lichenoid skin lesions. Records show that at least four of 11 cases of cus had skin lesions, whereas all had oral lesions. Stratified epithelium-specific antinuclear antibodies serve as the key marker of cus. Skin explants grown in the serum of this cus patient bind SES-ANA in tissue culture. Sections of explants fix complement. Titers of SES-ANA have been reported to parallel disease activity in one case, but not in the present case. Thus, there appears to be case-to-case variation. The treatment of choice for cus is hydroxychloroquine.

Necrotizing ulcerative gingivitis (NUG), necrotizing ulcerative periodontitis (NUP), and necrotizing stomatitis (NS), collectively termed necrotizing gingivostomatitis (NG), represent a dramatic, but rare oral infection associated with diminished systemic resistance, including HIV infection. Over a 5-year period, 68 consecutive NG patients from a population with known HIV status were evaluated and treated. Lesions were staged (modified Pindborg), and clinical findings and predictor variables were compared to 68 random control subjects without NG. Most cases (52%) were stage 1, with necrosis of the tip of the interdental papilla only; 19% were stage 2, with the entire papilla affected; 22% had necrosis of marginal (stage 3) or attached gingiva (stage 4); and 7% were more advanced, with mucosal necrosis or bone exposure. Attachment loss was a feature of stage 2 or greater NG. Beside HIV infection, significant predisposing factors included poor oral hygiene, unusual life stress, inadequate sleep, Caucasian race, age 18 to 21 years, and recent illness. Ten of 68 NG patients were HIV-positive. These patients were older than seronegative patients, less likely to be Caucasian, and maintained better oral hygiene and sleep. HIV-positive NG cases were clinically indistinguishable from HIV-negative cases in this series.

The purpose of this study was to investigate the pathogenesis of necrotizing ulcerative gingivo-periodontitis (ANUP) diagnosed in two brothers, age 9 (ANUP1) and 14 (ANUP2) from rural Egypt. Complete blood count, differential and blood chemistry were within normal limits for both brothers and they were not malnourished. The phagocytosis and killing function of their polymorphonuclear leukocytes (PMN) towards four bacterial species were assessed using a fluorochrome microassay. The selection of bacterial species was based on preliminary microbiological results in early onset periodontitis in Egypt. Fluorochrome-labeled Prevotella intermedia, Peptostreptococcus micros, Campylobacter rectus, and Porphyromonas gingivalis were pre-opsonized with ANUP serum and added to PMN from both ANUP patients, as well as PMN from three sex-matched and two sex- and age-matched healthy Egyptian control (CTL) subjects. We found significant depressions (P < 0.05) in PMN phagocytosis and killing of C. rectus and P. intermedia by ANUP1 and ANUP2, when compared to all CTL PMN. An assessment of the Gram-negative subgingival microflora present in both ANUP patients (in colony forming unit percent of total CFU recovered) (CFU %) revealed the presence of P. intermedia (ANUP1, 41.7 CFU %; ANUP2, 14.8 CFU %), Fusobacterium nucleatum (ANUP1, 3.6 CFU %; ANUP2, 48.1 CFU %), and Veillonella spp. (ANUP1, 18.2 CFU %; ANUP2, 18.5 CFU %). Spirochetes were also observed in cytocentrifuged, Gram-stained plaque from both ANUP patients. The predominant Gram-positive bacterial species recovered from both NUG1 and NUG2 was Streptococcus morbillorum.

Objective, reliable, and valid diagnostic criteria are required for studies of HIV-associated periodontal conditions. A set of diagnostic criteria were devised based on a literature review and the clinical experience of the authors. Validity was assessed by comparison with clinical photographs and the criteria were evaluated and refined for ease of use and objectivity. To assess the reliability of the criteria, 9 experienced examiners were shown 20 clinical photographs accompanied by brief vignettes of clinical information. Each examiner was asked to identify signs evident in a particular area of the photograph and to record a diagnosis. Five examiners were then trained and calibrated in the use of the criteria. Finally, all 9 examiners were shown the original 20 photographs and asked to identify signs and record diagnoses. The examiners showed only fair reliability in the recognition of clinical signs, made diagnoses intuitively, and had only fair agreement on the diagnosis of periodontal diseases. The inter-examiner reliability of examiners trained and calibrated in the use of the criteria increased and was greater than among untrained examiners. Rigid diagnostic criteria are essential in epidemiologic studies. Inter-examiner reliability will be increased if examiners are trained in their use and calibrated in the recognition of clinical signs. Diagnostic criteria should be modified as understanding of the diseases they classify increases. The proposed criteria will enhance the value of studies of HIV-associated periodontal changes and will contribute to that understanding.

Two hundred HIV-positive subjects were surveyed to determine their periodontal health status. Particular attention was given to the occurrence of a severe and rapidly progressing form of periodontal disease designated "HIV-associated periodontitis", which has been reported as being unique to AIDS patients. Among the subjects comprising the cohort, 85 subjects had good gingival health, 59 subjects exhibited gingivitis, 49 cases of adult periodontitis were observed, 5 subjects presented with advance adult periodontitis, and 2 cases of necrotizing ulcerative periodontitis (NUP) were found within the group. The periodontitis of the patients in this survey did not have unique or pathognomonic characteristics which could set their periodontal disease apart from the periodontal disease seen in HIV negative population.

Acute necrotizing ulcerative gingivitis (ANUG) has been generally considered as a gingivitis. However, clinical impressions suggest that periodontal attachment loss is one of the sequelae of the disease. This study was designed to investigate the extent of probing attachment loss detectable following resolution of the acute phase of the disease. 13 patients (3 male, 10 female) aged on average 22.7 years were studied. The presence of interdental soft tissue cratering was used to determine whether a site was previously affected by ANUG. ANUG sites were compared with other sites using a paired Student t-test (N = 13). Patient mean probing attachment level was greater for ANUG sites (2.2 +/- 0.9) than for the mean of all other sites (0.8 +/- 0.7). It is concluded that greater loss of probing attachment is associated with sites affected by ANUG than with other sites studied.

This study analyzed 58 cases of necrotizing ulcerative gingivitis (NUG) and 5 cases of cancrum oris among children who sought treatment at the Ibadan University College Hospital, Dental Centre in a 1-year period. The peak occurrence of NUG was among 4- and 5-year old children and 84.5% of them were in the 2 to 7 years age range. Seventy-two percent presented in the rainy season with positive history of recent febrile illness in 55 cases. There was no statistically significant association of NUG and rainy season. Possible predisposing factors in NUG and cancrum oris such as malnutrition, infectious childhood diseases, HIV infection, and immune compromise are discussed. It is suggested that children at risk should be advised to maintain good oral hygiene, adequate nutrition, and proper medical care.

The presence of spirochetes and other bacteria during the induction of necrotizing ulcerative gingivitis (NUG) in beagle dogs was studied by transmission electron microscopy. NUG was induced by application of dental debris from diseased dogs to 4 beagles treated with corticosteroid. Biopsies of interdental papillae were collected during a period of 7 weeks. Spirochetes and other bacteria were observed in enlarged intercellular spaces between non-keratinized epithelial cells. Intracellular bacteria were found with and without surrounding vesicular spaces. The invasive spirochetes were mainly intermediately sized and of flagellar "4-8-4" configuration or higher. Bacterial invasion of the sulcular epithelium occurred before clinical evidence of NUG could be observed. It is concluded that invasion by intermediate spirochetes and other bacteria plays a role in initiating ulcerative gingivitis in beagles.

Free cortisol concentrations in unstimulated whole saliva samples, collected at 10.00 to 11.00 h, from 23 unmedicated HIV-positive patients and 14 control subjects were measured by radioimmunoassay. Mean cortisol level (nmol/l +/- SD) was significantly higher in the HIV patients than in control subjects (27.4 +/0 9.3 vs. 10.1 +/- 3.5). Two HIV patients with pseudomembranous candidiasis had the highest saliva cortisol concentrations (mean of 48.5 nmol/l). Two other HIV patients (one with Kaposi's sarcoma and the other with periodontitis) had a mean cortisol value of 29.9 nmol/l. The possibility of plasma contamination of whole saliva in the HIV patients with inflammatory oral mucosal lesions notwithstanding, our findings suggest an increased oral burden of cortisol in both the asymptomatic and symptomatic HIV-infected individuals. Glucocorticoids caused immunosuppression, provide selective growth advantage to various microorganisms including the fungi, and enhance replication or reactivation of latent viruses (e.g. EBV, CMV, Kaposi's sarcoma-associated herpes viruses). Our findings suggest a need to evaluate the relevance of endogenous glucocorticoid excess in blood and saliva to the causation of some major AIDS-associated oral lesions such as candidiasis, Kaposi's sarcoma, oral hairy leukoplakia and necrotizing gingivitis.

A case is described of gingival non-Hodgkins lymphoma presenting in a site previously diagnosed as HIV-periodontitis. The lymphoma presented along with other signs of HIV infection and AIDS, which taken together were compatible with increased immunosuppression and reactivation of Epstein-Barr virus. The implications of these findings are discussed, and it is suggested that areas of gingiva which show rapid localised recession, associated with HIV seropositivity, should be monitored closely and considered for biopsy if abnormal signs are detected.

There are numerous correlations between features of acute necrotizing gingivitis (ANG) and virus infections, notably cytomegalovirus (CMV) infections. The age range of occurrence of seroconversions to CMV positive and occurrence of ANG correlate both in industrialized countries (young adults) and in underdeveloped countries (young children). A depression in cell-mediated immunity, as evidenced by a decrease in T-lymphocyte helper/suppressor ratio and decreased responsiveness to the mitogen ConA, has been shown to occur in both CMV infection and ANG. There is a higher incidence of both CMV infection and ANG in young male homosexuals. These and other correlations, taken together, argue for a fundamental role for virus in ANG etiology.

Adult cotton top marmosets made niacin deficient by long-term dietary deprivation, developed a syndrome characterized by anorexia, weight loss, weakness, diarrhea, dermatitis, enterocolitis and stomatitis. The stomatitis was highlighted by a necrotizing gingivitis and periodontitis and by an ulcerative and atrophic glossitis.

The induction and transmission of Necrotizing Ulcerative Gingivitis (NUG) lesions in beagle dogs have been reported previously. In the present experiments the contagious nature of these NUG lesions was further investigated by studying the unilateral induction and the intraoral transmission of NUG lesions. Six beagle dogs were treated with Kenacort A40®. The control quadrants of their dentition were cleaned while the experimental quadrants were not. The experimental quadrants were inoculated with pooled dental debris from the same dogs. NUG lesions were induced in the experimental quadrants, but NUG lesions were observed also at some sites of the control quadrants. In the second part of the experiment, reinoculation of non-affected experimental sites with debris from lesions of the same dog or cage companion increased the number of NUG lesions in both experimental and control quadrants. The study of experimental intraoral transmission of NUG lesions was restricted to the non-diseased sites in experimental and control quadrants. Topical application of debris of NUG lesions on the test sites did not spread the disease to these sites. Microscopic and cultural evaluation of subgingival microflora revealed no differences in the presence of Bacteroides, Fusobacteria, Spirocheata, and Spirillum in relation to the presence or absence of NUG. Three different types of black pigmental Bacteroides species were observed. It is concluded, that the morphology of the interdental sites is of great importance for the clinical occurence of NUG lesions and that the increase in number and severity of lesions after local reinoculation indicates that in the phase of primary infection, iatrogenic NUG lesions might be possible in a susceptible host.

This investigation was designed to gain information on the relative levels of salivary immunoglobulins in patients with acute necrotizing ulcerative gingivitis as compared to patients with clinically healthy gingival tissue. Relative levels of salivary immunoglobulins in diseased and healthy patients were measured and standard antisera to human immunoglobulins were used to detect any host antibody production in both parotid fluid and whole saliva. Salivary samples were analyzed for five classes of immunoglobulins: IgG, IgM, IgA, IgAsec, and IgE. Healthy individuals showed no detectable concentration of IgM or IgE in whole saliva or parotid fluid. IgG, IgA, and IgAsec were present in all samples. Individuals with acute necrotizing ulcerative gingivitis demonstrated no detectable concentration of IgM in whole saliva or parotid fluid, IgE in normal individuals was not detectable; therefore, it was not included in the acute necrotizing ulcerative gingivitis analysis. There was a decrease in parotid fluid conc...

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.

T H E R E IS A B U N D A N T evidence to implicate microorga­ nisms as the primary etiologic agents of various forms of periodontal disease (for reviews see 1 6 ) . Particularly convincing were the demonstrations by Loe and co­ workers that removal of dental plaque by rigorous plaque control procedures 7 , 8 or antiseptic agents 9 , 1 0 could prevent or reverse clinical gingivitis in human volunteers. More recently, Lindhe and Nyman 1 1 and Rosling et a l . 1 2 demonstrated that progress of destruc­ tive periodontitis could be halted and partially reversed by surgical procedures when accompanied by twice monthly professional tooth cleaning. These studies in­ dicated that suppression of the total microbiota could be effective in controlling both gingivitis and destruc­ tive periodontitis in humans. What the studies did not and could not indicate is whether all or only segments of the microbiota were responsible for the observed clinical response. The success of antibiotic therapy in controlling the acute phase of acute necrotizing ulcera­ tive gingivit is 1 3 1 7 indicates the etiologic role of micro­ organisms in this form of human periodontal disease. Since only some of the species resident in bacterial plaque are sensitive to a given antibiotic, it is clear that only a finite segment of the microbiota is responsible for this disease. It would seem that there is sufficient evidence that microorganisms play a primary role in the etiology of most forms of human periodontal disease. The question is no longer whether organisms cause periodontal dis­ eases but rather are specific organisms responsible for specific disease forms?

The devastating orofacial gangrenous disease known as cancrum oris (noma) is still commonly seen in underprivileged Nigerian children. These children are usually victims of such stressors as chronic malnutrition, numerous endemic communicable diseases and severe adverse physical conditions which may lead to depletion of their adaptive resources or produce physiological maladaptation to additional stressors. Measles is the most common infection preceding the development of noma in Nigerian children. Acquired immunodeficiency as well as the impaired endocrine balance of the chronically malnourished permits, for example, widespread infection with the measles virus. Anergy resulting from the combination of malnutrition and measles virus infection promotes selective overgrowth and invasion by an infective consortium consisting of anaerobic organisms and other species capable of elaborating necessary growth factors for the former. Because of the pre-existing depletion of adaptive physiologic resources in the malnourished child, the infection is not readily contained locally as necrotizing ulcerative gingivitis but instead spreads rapidly to the next naturally occurring anatomical barriers. This is then followed by continuing necrosis and possible sequestration as exemplified by noma.

— A case of acute ulcerative gingivitis (AUG) with pericoronitis is presented showing how differential dark‐field microscopy can be used to aid in diagnosis and monitor therapy. The AUG site showed a unique flora with dark‐field microscopy, which in this case was shared by the pericoronitis lesion. Metronidazole therapy resulted in a marked change in the flora of both sites. Four days following therapy both sites showed a similar flora to a normal healthy site which remained unaltered throughout the treatment. 1985 Australian Dental Association

Superficial ulcerations of the oral mucosa often present a diagnostic challenge to the physician because of the similarity of one ulcer to another. A diagnosis is made by the analysis of multple factors, including the lesion's location, size, grouping, onset, patient's age, involvement of other systems of the body, and course of the disease. The histopathology of the lesion may be specific, especially in certain potentially fatal diseases. This paper presents the means for the differential diagnosis of a variety of superficial ulcers of the oral mucosa: varicella, herpangina, recurrent aphthous stomatitis, Behçet's disease, Stevens-Johnson syndrome, traumatic ulcer, verrucous carcinoma, primary herpetic gingivostomatitis, recurrent herpetic stomatitis, pemphigus vulgaris, and benign mucous membrane pemphigoid.