Search

Objective Oral hairy leukoplakia (OHL) is a benign Epstein-Barr virus infection typically presenting as a white lesion on the lateral border of the tongue. Historically, OHL was described in patients who are severely immunocompromised, such as those with HIV/AIDS and organ transplant patients. OHL is increasingly seen in patients who are not severely immunocompromised. This study reviews 45 cases of OHL in a single institution and characterizes the clinical features of these relatively immunocompetent patients. Study Design Retrospective study. Results There were 45 cases with 23 male patients (51.1%) and a median age of 64 (range, 24-100 years). The lateral/ventral tongue was the affected site in 41 cases (91.1%), and 5 cases presented bilaterally. A review of the medical history and medications showed the most common conditions were hypertension (53.3%), hyperlipidemia (42.2%), and chronic respiratory conditions (33.3%); 8 patients (17.8%) had diabetes mellitus, and 1 had rheumatoid arthritis. Eleven cases (24.4%) reported no underlying medical conditions or history of medications. The most frequently reported medications included antihypertensive drugs (21.0%), steroid inhalers (14.6%), and cholesterol-lowering drugs (11.0%). Conclusions OHL is not exclusively seen in profoundly immunocompromised patients. Localized immunosuppression (from steroid inhalers) and immunosenescence (aging) are possible contributing factors.

Oral hairy leukoplakia (OHL) is an Epstein-Barr virus (EBV) related lesion seen in severely immunocompromised patients especially, those with concomitant human immunodeficiency virus (HIV) infection. It has been rarely reported in immunocompetent patients. OHL most often presents on the lateral border of the tongue as an asymptomatic, white, and corrugated plaque that does not rub off. With Institutional Review Board (IRB) approval, the University of Florida Oral & Maxillofacial Pathology Biopsy Service archives spanning 1994–2020 were queried. All cases of OHL affecting immunocompetent patients were identified. Data related to age, gender, clinical presentation, results of Epstein-Barr virus in situ hybridization (EBER-ISH), and periodic acid–Schiff (PAS)-fungus stains were recorded. Medical history and histology of all cases were reviewed for confirmation of diagnosis. A total of 11 cases were identified, the majority of which were males (63.6%) with a mean age of 62 years. All patients were Caucasian. Lesions entirely were located on the lateral borders of the tongue. OHL should not be considered pathognomonic for HIV infection and should be included in the differential diagnoses of keratotic lesions affecting the lateral border of tongue even in immunocompetent elderly patients. The etiology of OHL in this group of patients is not clearly understood.

The significance of the oral manifestations of HIV has been widely recognised since the start of the epidemic. It is estimated that more than 38 million people are living with HIV currently, with more than a third presenting with oral manifestations. Access to optimum clinical management and effective treatment in resource-rich countries has led to a remarkable decrease in some of the oral manifestations in the HIV population but this is not mirrored in developing countries, where most HIV-positive patients reside. In this paper, a review of the literature since the start of the HIV infection in different parts of the world is presented to highlight the current significance of the oral conditions in this population. Oral candidiasis was repeatedly reported as the most encountered oral manifestation of HIV in different countries, including in studies on groups on anti-retroviral therapy. Over time salivary gland disease was reported less in developed countries but was encountered more in developing countries. There is evidence to show that the prevalence of oral warts increased with the establishment of anti-retroviral therapy. A review of the worldwide prevalence of HIV-related oral conditions indicates that except for oral hairy leucoplakia, the prevalence of all other nine commonly reported oral conditions remained the same or increased over time. Oral opportunistic infections in HIV-infected patients are an ongoing clinical burden mainly in developing countries. Maintaining research in the subject and improving access to HIV treatment will help address the oral health inequalities around the world.

Objective To review the existing research literature on the paradigm that the oral lesions could be an indicator of the disease severity with the objective of documenting the current status of research, highlighting its major findings. Material and methods Publications were identified through a careful search, of which a majority focused on oral lesions as an indicator for HIV progression. A PubMed journal search of 10 years OF period publication (2009-2019) for "oral lesion, oral manifestation, indicator, HIV and HIV-associated" was performed and analysed. Various research methods were included within the study criteria including clinical study, clinical trial, comparative study and randomised control trial. Results A total 33 studies were obtained and analysed, including cohort study, cross-sectional study, case-control study, clinical trial, retrospective observational analysis study, prospective observational study and randomised control trial. The most common oral lesions found in the studies were Kaposi sarcoma (KS), followed by oral candidiasis, periodontitis, necrotising ulcerative gingivitis (NUG), necrotising ulcerative periodontitis (NUP) and oral hairy leucoplakia (OHL). The early diagnosis and accurate treatment plan were very important to indicate the disease severity related to HIV infection. Conclusion Oral lesions reported in 39% articles and could be an indicator of HIV disease severity due to its effects on decreased cluster-differentiated (CD4+) T-cell count and increased viral load.

We present three cases of oral hairy leukoplakia (OHL) in whom the diagnosis was established by EBV DNA detection in whole saliva. Three HIV-infected patients came to the Oral Medicine Clinic with similar chief complaints of asymptomatic white lesions on the tongue. All patients were diagnosed with suspected OHL and oral thrush also in the first patient. A multiplex PCR DNA microarray was performed to detect EBV DNA in saliva collected by spitting method. All saliva samples showed positive results for EBV DNA, and the definitive diagnosis of OHL was made. Resolution of lesions was found at 1- to 2-month follow-up after treatment with application of acyclovir 5% cream 5 times daily. Additionally, anti-fungal treatment was given to the first patient and anti-retroviral treatment to the first and second patients. EBV is mostly transmitted by asymptomatic shedding into saliva. Therefore, the detection of salivary EBV DNA is useful in establishing a definitive diagnosis of OHL allowing more effective treatment for both HIV-infected patients receiving ART and treatment-naive patients at any CD4 + count.

Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that establishes a lifelong persistent infection in the oral cavity and is intermittently shed in the saliva. EBV exhibits a biphasic life cycle, supported by its dual tropism for B lymphocytes and epithelial cells, which allows the virus to be transmitted within oral lymphoid tissues. While infection is often benign, EBV is associated with a number of lymphomas and carcinomas that arise in the oral cavity and at other anatomical sites. Incomplete association of EBV in cancer has questioned if EBV is merely a passenger or a driver of the tumorigenic process. However, the ability of EBV to immortalize B cells and its prevalence in a subset of cancers has implicated EBV as a carcinogenic cofactor in cellular contexts where the viral life cycle is altered. In many cases, EBV likely acts as an agent of tumor progression rather than tumor initiation, conferring malignant phenotypes observed in EBV-positive cancers. Given that the oral cavity serves as the main site of EBV residence and transmission, here we review the prevalence of EBV in oral malignancies and the mechanisms by which EBV acts as an agent of tumor progression.

Oral hairy leukoplakia (OHL) is caused by Epstein-Barr virus (EBV) and is often associated with HIV and other immunosuppressive conditions. It is rare in HIV-negative patients, but has been reported in patients who use immune-modulating medications (e.g., cyclosporine). The objectives of this study were to determine the occurrence of OHL in HIV-negative patients and report Langerhans cell counts in these lesions.A series of 7 new cases of OHL among HIV-negative patients is described. Langerhans cells were counted using an immunoperoxidase stain for CD1a and light microscopy.The 7 patients were male, ranging in age from 26 to 69 years. Clinically, all lesions were diagnosed as leukoplakia on the lateral border of the tongue. Microscopic examination revealed hyperparakeratosis and candidiasis in some cases, acanthosis and a band-like zone with clearing of cells in the upper spinous layer, which were EBV-positive by in-situ hybridization. There was a significant decrease in Langerhans cell counts in OHL patients.OHL can occur in HIV-negative patients.

Background Because of reduced mortality, patients with HIV are living longer and presenting with chronic diseases. Little is known about racial differences in dermatologic conditions associated with HIV infection. Objective This study examines associated dermatologic conditions in a large population of patients with HIV at a tertiary care center with a diverse patient population. Methods Cross-sectional study of patients with HIV seen between July 14, 2013, and July 14, 2018, in a tertiary health care system. The burden of HIV-related dermatologic conditions was collected by using medical records. Patients with HIV were compared with control individuals of the same race, and significance was assessed using the chi-square test. A Bonferroni correction was performed to control for multiple hypothesis testing. Results The study population (N = 4679) was 64.7% male and 69% African American, with 88.7% of patients receiving antiretroviral therapy. African American patients with HIV had a greater risk of oral hairy leukoplakia (odds ratio [OR], 64.49), herpes zoster (OR, 9.27), prurigo nodularis (OR, 8.80), and squamous cell carcinoma (OR, 5.72). Limitations Our data describe patients seen by 1 health care system. Conclusions African American patients with HIV may be at increased risk for pruritic disorders compared with race-matched control individuals and white patients with HIV.

Well into the fourth decade of the HIV/AIDS pandemic, we can look back on the early years, the initial discoveries, and the broad sweep of the progress of our understanding of the nature, causes, and significance of the oral lesions seen in those infected with the virus. Prominent among these is oral hairy leukoplakia (HL), a previously unknown lesion of the mouth associated with Epstein-Barr virus (EBV) and initially seen only in people with AIDS, in the then-recognized risk groups, or those shown to be HIV positive. Subsequently, it became clear that the distribution of HL extends well beyond the HIV spectrum. In this brief review, we consider the clinical and histological features of HL, discuss how it was discovered, explore its cause, diagnosis, relationship with AIDS, pathogenesis, significance in EBV biology, options for management, and how it changes with HIV/AIDS therapy.

Oral hairy leukoplakia (OHL) is caused by the Epstein-Barr virus (EBV) and usually presents in patients with human immunodeficiency virus (HIV) infection and systemic immunosuppression. It is rarely seen in patients who are immunocompetent. It is clinically characterised as an asymptomatic, soft, white and corrugated lesion that cannot be scraped from the surface it adheres to. Immunocompetent patients with OHL attending Bristol Dental Hospital within the last 6 months were identified. EBV infection was demonstrated using EBV in situ hybridization. Clinical features and medical history were determined by reviewing medical records. Four cases of OHL in immunocompetent individuals were identified. All lesions were located on the lateral borders of the tongue. OHL should be considered as a differential diagnosis for white patches on the lateral borders of the tongue in apparently healthy immunocompetent patients, even when they do not have a typical corrugated appearance. OHL should no longer be regarded as pathognomonic for HIV infection or systemic immunosuppression.

Permanent immunosuppression is necessary to prevent rejection after kidney transplantation. However, it may predispose patients to different conditions and diseases including oral lesions. The most common benign oral lesions in kidney transplant recipients are gingival hyperplasia, oral candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma, although rarely, can also be seen in kidney transplant patients. In this review, we present the incidence, etiology, clinical findings, diagnosis and treatment options for these lesions. For kidney transplant recipients, it is important to maintain good oral hygiene and care, as well as regular professional control by the dentist. This approach can reduce the number and severity of oral lesions.

Objective We report here the 10-year experience with oral hairy leukoplakia (OHL) at the Division of Oral and Maxillofacial Pathology at the University of North Carolina at Chapel Hill, NC, USA. Study Design All the associated hematoxylin and eosin and Epstein-Barr virus encoding region in situ hybridization slides of OHL cases between January 1, 2008, and February 1, 2017, were retrieved and reviewed. Collected demographic characteristics, clinical presentation, medical and social histories were reviewed and reported. Results Six OHL cases with confirmed in situ hybridization showed predilection for the lateral tongue. The study included 3 females and 3 males (mean age 50.5 years; age range 29-70 years). One patient had known HIV-positive status before biopsy was performed. Three patients had reported a history of heavy smoking. Other medical conditions reported were history of breast cancer, a long history of corticosteroid inhaler use for asthma treatment, high cholesterol, diabetes, and hypertension. Conclusions The findings of this study indicate the need to include OHL as a potential entity in the differential diagnosis of leukoplakic tongue lesions, regardless of the patient's HIV status. In addition, the presence of OHL in the patient requires investigation of various explanations for EBV infection, including immunosuppression caused by HIV infection or chronic steroid use.

Author(s): Braz-Silva, Paulo Henrique; Schussel, Juliana Lucena; Lopez Ortega, Karen; Gallottini, Marina | Abstract: Background: Oral hairy leukoplakia (OHL) is a benign lesion caused by Epstein-Barr virus (EBV) replication in the oral epithelium affecting the borders of the tongue. It is strongly associated with immunosuppression, especially in HIV+ adults but is uncommon in pediatric population. The aim of the study is to show the importance of the correct diagnosis of OHL and its influence on HIV treatment.We report two cases of HIV+ adolescent patients that presented with leukoplakic lesions on the border of the tongue, suggestive of OHL. OHL diagnosis was confirmed in only one case through EBV in situ hybridization. After confirmation of the diagnosis, the patient with OHL was referred to an infectious disease specialist with the decision to start antiretroviral therapy. Conclusion: OHL definitive diagnosis can help clinical management of pediatric HIV+ patients.

Background Human immunodeficiency virus (HIV) infection is a major global health problem. Tuberculosis and cryptococcal meningitis are the leading cause of death among people living with HIV. Aim The purpose of this study was to determine whether any relationship exists between the occurrence of oral lesions and opportunistic infections among HIV-infected patients in Indian population. Materials and methods A cross-sectional analytical study was performed in 232 HIV-infected persons (148 males and 84 females, aged 20-60 years, mean 33.6 ± 2.3 years). c2 test and logistic regression were used for statistical analysis. Results Oral candidiasis was the most common oral lesion seen in 28.4% males and 22.6% females of HIV-infected persons, followed by hairy leukoplakia in 27% males and 20.2% females which was statistically significant. Tuberculosis (21.6%) followed by cryptococcosis (9.9%) and pneumocystis carinii pneumonia (4.7%) were the most commonly found opportunistic infections. Logistic regression analysis revealed a significant association, between the occurrence of tuberculosis and candidiasis (OR 2.3; 95% CI 1.4-2.9), cryptococcosis and candidiasis (OR 1.4; 95% CI 1.0-1.9), and pneumocystis carinii pneumonia with hairy leukoplakia (OR 1.6; 95% CI 1.0-2.9). Mean CD4 count was also less. Conclusions The results suggest a definite relationship in occurrence of oral lesions and opportunistic infections among HIV-infected patients.

Proliferative verrucous leukoplakia (PVL) is a rare less recognized form of oral leukoplakia. Patients with this condition represent a unique clinically and pathologically progressive characteristic from conventional leukoplakia. Because of the lack of defined pathologic lesions, identifying patients with the early diagnosis of PVL is challenging. This is largely due to the overlapping clinical and pathologic early features with conventional multifocal leukoplakia with dysplasia. The diagnosis can only be achieved through the keen clinical observation of the temporal progression in individual patients to verrucous and/or conventional squamous carcinoma. We present a brief view of the clinicopathologic and biological characteristics of PVL and discuss diagnosis, differential diagnosis, and management.

Aim: The purpose of this study was to compare gender differences in the prevalence of oral lesions in HIV-infected Brazilian adults. Methodology: A retrospective study was conducted of medical records from HIV/AIDS patients from 1993 to 2004. Oral lesions were only included in this study if definitively diagnosed through microscopic analysis, therapeutic test or according to EC-Clearinghouse criteria. Results: A total of 750 men and 237 women were included in the study. Statistically significant differences were observed only for oral hairy leukoplakia, Kaposi sarcoma and lymphadenopathy (P < 0.01). However, a model of logistic regression showed that only oral hairy leukoplakia presented a significant association with gender and males had a significantly likelihood (four times higher than females) of presenting with this oral manifestation [OR 4.3 (95% CI: 1.39–13.36)]. Conclusion: These data shows that oral manifestations are less prevalent in females than in males, particularly oral hairy leukoplakia.

We report the case of a 31-year-old woman with systemic lupus erythematosus who was found to have oral hairy leukoplakia (OHL). She was on immunosuppressive therapy but was human immunodeficiency virus (HIV)-negative. OHL has been previously reported in HIV-negative patients who were immunosuppressed for other reasons, such as solid organ or hematopoietic stem cell transplantation, hematologic malignancies, or systemic diseases. To the best of our knowledge, this is the first case of OHL in an HIV-negative patient reported in the otolaryngology literature. It adds to the growing list of cases of OHL in HIV-negative patients and serves as a reminder to physicians to include OHL in the differential diagnosis for oral cavity lesions in all immunosuppressed patients. The article also summarizes the current state of knowledge about the pathogenesis of OHL, its relation to the Epstein-Barr virus, and the treatment options.

Objective To establish a definitive diagnosis of oral hairy leukoplakia (OHL) by in situ hybridization for Epstein–Barr virus (EBV) detection with liquid-based cytology (LBC), using the ThinPrep® Pap Test, and to compare its efficacy with the traditional method of performing biopsy. Methods Thirty-three individuals divided into three groups were included in this study. Group 1 consisted of 15 human immunodeficiency virus (HIV)-positive patients with a clinical and histopathological diagnosis of OHL on the lateral border of the tongue. Group 2 consisted of 10 HIV-positive individuals with neither OHL nor other oral lesions. Group 3 consisted of 10 immunocompetent HIV-negative individuals with neither OHL nor other oral lesions. For each patient from the three groups, exfoliative LBC was performed on the lateral border of the tongue using ThinPrep. For the patients from group 1, a 6-mm-diameter punch biopsy was obtained from the same anatomic site as the brush collection to confirm the diagnosis of OHL by histopathology with in situ hybridization. Slides were prepared for morphological cellular analysis using Papanicolaou (Pap) staining, and for EBV detection using in situ hybridization. Results Thirteen of the 15 patients from group 1 were confirmed on punch biopsy as OHL, providing the gold standard for the study. The sensitivity of LBC followed by a Pap-stained smear was 62% and the specificity was 90%. The sensitivity of LBC followed by in situ hybridization was 100% and the specificity was 100%. Conclusions Exfoliative LBC associated with EBV in situ hybridization is a simple, effective and non-invasive diagnostic tool for OHL.

The tongue is a complex organ involved in speech and expression as well as in gustation, mastication, and deglutition. The oral cavity, along with the tongue, are sites of neoplasms, reactive processes, and infections, and may be a harbinger of systemic diseases. This review includes both common and rare diseases that occur on the tongue, including: vascular and lymphatic lesions (infantile hemangiomas and oral varices), reactive and inflammatory processes (hairy tongue, pigmented fungiform papillae of the tongue, benign migratory glossitis, and fissured tongue), infections (oral hairy leukoplakia, herpes simplex and varicella-zoster virus infections, human papillomavirus, and candidiasis), premalignant lesions (leukoplakia and erythroplakia), malignant lesions (squamous cell carcinoma, Kaposi sarcoma, and lymphoproliferative diseases), and signs of systemic disease (nutritional deficiency and systemic amyloidosis).

Permanent immunosuppression is necessary to prevent rejection after kidney transplantation. However, it may predispose patients to different conditions and diseases including oral lesions. The most common benign oral lesions in kidney transplant recipients are gingival hyperplasia, oral candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma, although rarely, can also be seen in kidney transplant patients. In this review, we present the incidence, etiology, clinical findings, diagnosis and treatment options for these lesions. For kidney transplant recipients, it is important to maintain good oral hygiene and care, as well as regular professional control by the dentist. This approach can reduce the number and severity of oral lesions.

Permanent immunosuppression is necessary to prevent rejection after kidney transplantation. However, it may predispose patients to different conditions and diseases including oral lesions. The most common benign oral lesions in kidney transplant recipients are gingival hyperplasia, oral candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma, although rarely, can also be seen in kidney transplant patients. In this review, we present the incidence, etiology, clinical findings, diagnosis and treatment options for these lesions. For kidney transplant recipients, it is important to maintain good oral hygiene and care, as well as regular professional control by the dentist. This approach can reduce the number and severity of oral lesions., Nakon transplantacije bubrega bolesnici moraju biti na trajnoj imunosupresiji, što ih čini osjetljivima za različita stanja i bolesti uključujući oralne lezije. Najčešće dobroćudne oralne lezije kod bolesnika s transplantiranim bubregom su hiperplazija gingive, oralna kandidijaza, vlasasta leukoplakija i obloženi jezik. Oralna forma Kaposijevog sarkoma također se, iako rijetko, može vidjeti kod bolesnika s transplantiranim bubregom. Donosimo pregled incidencije, etiologije, kliničke slike, dijagnoze i liječenja ovih lezija. Kod bolesnika s transplantiranim bubregom važna je redovita skrb za oralno zdravlje uz održavanje oralne higijene te redovite posjete liječnicima dentalne medicine, što sve može smanjiti broj i ozbiljnost oralnih lezija.

Oral lesions are common in human immunodeficiency virus (HIV)-infected patients, which may indicate impairment of the patient’s general health status, and, in many cases, the oral lesions are the first sign of an HIV infection. Oral hairy leukoplakia (OHL) is a benign lesion of the oral mucosa related to Epstein-Barr virus (EBV) observed in HIV-positive individuals. The aim of this study was to report the contribution of oral cytopathology in the investigation of the HIV/AIDS status of patients as well as in the clinical and subclinical identification of OHL. Three patients were referred to the Oral Medicine Clinic in 2010. The patients were submitted to oral examination, and scrapes of the tongue were obtained. The Papanicolaou staining technique was used, and cytopathological analysis showed nuclear changes corresponding to cytopathic effects of EBV epithelial infection and candidiasis. The final diagnosis was OHL and candidiasis. Based on cytopathological diagnosis, an HIV serologic test was requested which revealed positive HIV serology. None of the patients was aware of their HIV serological status, and thus the cytopathology, by identifying OHL, contributed to the early diagnosis of HIV/AIDS. Cytopathology should be used as a routine procedure and it may be the method of choice for clinical and subclinical OHL diagnosis.

We describe a case of oral hairy leukoplakia that presented with an atypical appearance in a patient on long-term anticonvulsant treatment with an aromatic antiepileptic, lamotrigine. Recent medical history was also significant for recurrent respiratory tract infections requiring treatment with oral antibiotics. Immunologic investigations revealed inverted CD4/CD8 ratio, mild hypogammaglobulinemia, and poor specific antibody titers. Combined immune deficiency caused by long-term treatment with lamotrigine was suspected after other known factors and conditions (including retroviral infection) leading to acquired immune deficiency were excluded. Withdrawal of lamotrigine resulted in complete resolution of oral hairy leukoplakia. There was no significant improvement in immunoglobulin levels. The effect of lamotrigine and other aromatic antiepileptics on the immune system should be considered in a patient presenting with otherwise unexplained oral hairy leukoplakia.

We estimated the prevalence of oral lesions associated with human immunodeficiency virus (HIV-OLs) before and during the antiretroviral therapy (ART) era. The first period was 1997, when many patients received two types of antiretroviral (ARV) drugs. The second study period was 2004 through 2008, when all patients were treated with ART (a combination of two or three classes of drugs, including protease inhibitors). A total of 148 and 388 seropositive participants were examined in 1997 and 2004-2008, respectively. The evaluation consisted of anamnesis and physical examination. The prevalence of HIV-OLs decreased between 1997 (60.1%) and 2004-2008 (29.9%). The HIV-OL responsible for the greatest reduction in prevalence between the two periods was oral candidiasis, of which erythematous candidiasis was the clinical form that decreased most, followed by pseudomembranous candidiasis. In conclusion, we observed a significant reduction in HIV-OLs, which was closely associated with the use of ART. In addition, among patients with a clinical diagnosis of AIDS, we confirmed a significant reduction in HIV-OL prevalence between 1997 and 2004-2008.

Oral hairy leukoplakia (OHL) presents as a white, plaque-like lesion typically occurring on the lateral border of the tongue. This condition is caused by the Epstein-Barr virus, a human herpesvirus that often establishes lifelong, asymptomatic latent infection. OHL, initially described in immunocompromised men infected with the human immunodeficiency virus (HIV), has also been described in other severely immunocompromised patients. Only rarely has OHL been reported in less profoundly immunocompromised patients primarily in the setting of corticosteroid therapy. Here we report on two additional cases of OHL attributable to immunosuppressive medications.

The purpose of the present study paper was to review the reported prevalence of the oral manifestations of HIV (OM-HIV) worldwide since 1980, and to determine the global variation in its prevalence over time. PubMed, Scopus, Embase and Google Scholar were searched. The filter "English" was used. The timeframe searched was 1980- 2015. The PRISMA flow chart was used. Data were extracted using the Joanna Briggs Institute standardized data extraction form and transferred to SPSS version 22 for analysis. The systematic review of 97 studies (70 low bias risk) showed that the prevalence of OM-HIV continue to be significant in developing countries. Globally and through all the decades, oral candidiasis remained the most commonly encountered OM-HIV, including among patients on antiretroviral therapy (ART) (26.2%). Hairy leukoplakia was more prevalent in Europe and America compared with Africa and Asia. Oral warts were reported more often in studies on patients receiving ART. Interestingly, salivary gland disease decreased in the developed world and increased in developing countries over time. Despite the changing pattern of these conditions over time, there is no evidence that the OM-HIV have become of less significance globally. Maintaining the drive for high-quality research in the subject will have an impact on less developed countries to help address oral health inequalities.

Purpose: To determine the prevalence of Epstein Barr Virus (EBV) in oral hairy leukoplakia lesions (OHL) in HIV+ Venezuelan patients. Material and Method: In this case study, we evaluated 21 HIV+ adult patients with clinically present OHL lesions, 11 who were undergoing antiretroviral therapy, 10 who were not undergoing therapy and 10 HIV-negative adult patients with hyperkeratotic oral mucosal lesions. All of the subjects were assessed at the Infectious Disease Center, Faculty of Dentistry, Central University of Venezuela, and were clinically examined to detect oral mucosal lesions with the confirmed histopathologic diagnosis. Nested-PCR was used to determine the EBV infection and the latent membrane protein-1 (LMP-1) expression by immunohistochemistry. Results: Of the subjects, 16/21 (76%) of the HIV+/AIDS patients tested positive for EBV, whereas 5/10 (50%) of the HIV-negative subjects tested positive for EBV. Conclusions: In the present study, a higher EBV prevalence was observed in HIV-positive patients when compared to HIV-negative patients without oral hairy leukoplakia, confirming the etiologic role in this entity. The LMP-1 in OHL patients who were both HIV+ and EBV+ was highly expressed (60%) at the epithelial basal cells. No association between the alcohol and tobacco consumption was observed among the EBV-positive cases.

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.

OBJECTIVE: Oral hairy leukoplakia (OHL) is a white lesion of the tongue that is caused by Epstein-Barr virus (EBV) and occurs mainly in people infected with human immunodeficiency virus (HIV). The aim of this study was to determine whether the presence of OHL reflects the absence of EBV-specific cytotoxic T lymphocyte (CTL) activity. SUBJECTS AND METHODS: EBV-specific CTL responses were measured in HIV-positive homosexual men with OHL, HIV-positive homosexual men without OHL, and HIV-negative homosexual men. Also, the phenotypes of cells responsible for EBV-specific responses were studied. RESULTS: Eighty percent (8/10) of HIV-positive subjects with OHL, 52% (12/23) of HIV-positive subjects without OHL, and 83% (15/18) HIV-negative subjects had a positive anti-EBV CTL response (P= 0.004, Kruskal-Wallis test). Two HIV-positive subjects showed a greater anti-EBV CTL response after developing OHL than before the appearance of OHL. Additional experiments showed that CD8-positive T cells and CD4-positive T cells were responsible for the EBV-specific CTL responses. CONCLUSION: Our data show more EBV-specific CTL activities in HIV-positive individuals with OHL than in HIV-positive individuals without OHL. Whether the presence of EBV-specific CTL contributes to resolution of OHL remains to be clarified.

OBJECTIVE To test the hypothesis that the anti-apop totic ability of Epstein-Barr virus (EBV) may result in altered expression of apoptosis-associated proteins in oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for these proteins by immunohistochemistry. MATERIALS AND METHODS Twenty formalin-fixed, paraffin-embedded specimens of HL lesions and six spedmens of normal control mucosa were selected from archived tissue specimens. Bcl-2. Bcl-x, Bax and p53 apoptoris-associated proteins were evaluated in immu-nohistochemically stained tissue sections according to staining intensity and pattern. The percentage of p53-positive burl cells was estimated in sequential fields. RESULTS: Generalty, there were only slight differences in the expression of Bcl-2 and Bcl-x proteins in the epithelium of HL and control tissue. The staining for Bcl-2 was weaker in keratinocytes than in putative melano-cytes and Langerhans cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted. Keratinocytes throughout the epithelium stained positively for Bcl-x protein, although upper layers were more weakly stained. The ‘balloon’ keratinocytes in HL were infrequently positive for Bcl-x. Bax staining in HL differed from that in control tissue in being more heterogeneous. The staining reaction in HL was weak to negative in upper epithelial levels where ‘balloon’ keratinocytes were located. Weak to moderate nuclear p53 protein staining was detected in a mean of 25.3% of basal keratinocytes in all but one of the HL specimens; weak staining was seen in only two control specimens. CONCLUSIONS: We found only slight immunohistochemid evidence that expression of the apoptosis-associated proteins is altered in HL. p53 appears to be over-expressed in HL; we speculate that this may be related to upregulation or stabilization of wild-type p53 protein related to EBV infedon.

OBJECTIVES: Examine variations in oral manifestations of HIV by gender, race, risk behaviors, substance use and immune status in a previously unstudied population in the southeast region of the USA. DESIGN: Cross-sectional analytic study. SETTING: Academic medical center, North Carolina, USA. SUBJECTS: First 238 HIV-infected adults (76% male; 59% Black) enrolled in an ongoing longitudinal study. METHODS: Oral examination, medical chart review, sociodemographic and behavioral interview. Descriptive, bivariate, and multivariable analyses. OUTCOMES: Presence of oral manifestations of HIV. RESULTS: 50% had recent CD4 counts

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.

The first case of oral hairy leukoplakia (OHL) in an HIV-negative 56-year-old patient with acute lymphocytic leukemia (ALL) is reported. A white plaque was observed while the patient was in complete remission which followed the chemotherapeutic scheme. The clinical and histopathologic findings were typical for OHL and the polymerase chain reaction method was positive for Epstein-Barr virus DNA. Underdiagnosis and underreporting of OHL in patients with a malignant haematological disease and the apparent different environmental factors to which these non-AIDS patients have been exposed, probably constitute some of the reasons for the very few OHL cases reported in these patients.

Objective: The purpose of this study was to determine the prevalence of the oral manifestations of HIV/AIDS and to correlate the prevalence of these lesions with the stages of the disease in the Ife-Ijesa zone, Nigeria. No comprehensive data were available for correlating it with the staging of HIV/AIDS in this region. Subjects: The pattern of oral HIV lesions as classified by the EC-Clearinghouse was studied in 225 confirmed consecutive HIV-infected patients in this zone. Methods: Clinical dental examinations were conducted under natural daylight on all consenting HIV patients, sitting in an upright chair, using dental mirrors and probes. Results: The prevalence of oral HIV lesions was 84.0%, with lesions ranging in number from one to six. The commonest HIV lesion was pseudo-membranous candidiasis (43.1%) followed by erythematous candidiasis (28.9%), angular cheilitis (28.9%), linear gingival erythema (24.0%) and ulcerations (8.9%). Lesions less commonly found were oral hairy leukoplakia (1.3%) and salivary gland swellings (1.3%). Heterosexual intercourse was the most common mode of transmission (94.7%) and HIV-1 (96.9%) the most prevalent pathogen among the study population. The majority of the patients were in the WHO clinical stage III (59.1%) and presented late. Conclusions: The prevalence of oral HIV lesions in the present study was high.

The objectives were to estimate oral disease prevalence among Zimbabwean women by HIV serostatus and CD4 cell count and to assess accuracy of oral disease diagnoses made by nurses as compared with an oral surgeon. Standardized oral mucosa examinations were performed by trained nurse-examiners and by an oral surgeon among women recruited in Harare Zimbabwe. A total of 461 women (320 HIV-infected 141 uninfected) were seen by nurses and an oral surgeon within a 2-week period. Oral candidiasis (OC) was the most common lesion diagnosed in nearly one quarter of HIV-infected women whereas hairy leukoplakia and Kaposi sarcoma were found in less than 3%. The prevalence of OC diagnosed by nurses or the surgeon was significantly higher among women with a CD4 count less than 200 cells/mm3 than in women with a CD4 count from 200 to 499 cells/mm3 or a CD4 count greater than 499 cells/mm3. The sensitivity of nurse examinations compared with examinations by the oral surgeon among HIV-infected women for the diagnosis of OC was 73% the specificity was 95% and the k-statistic was 0.71. OC was the most common lesion in HIV-infected women and was strongly associated with a low CD4 cell count. Interexaminer agreement was good for the diagnosis of OC among HIV-infected women. This study suggests that OC may play a role in combination with other clinical indicators as a marker of disease progression in resource-poor settings. (authors)

Histopathological findings in cases of hairy leukoplakia (HL) are not exclusive to this lesion. A total of 36 tissue samples from patients previously diagnosed with HL based solely on morphological aspects were used in this study. Our purpose was to confirm the presence of Epstein–Barr virus (EBV) in these tissue samples by in situ hybridization (ISH), and to compare the detection of EBV with specific histopathological findings observed in each case. Among the 36 specimens, 80.55% were EBV positive, confirming the previous clinical and histhophatological diagnosis. None of the histopathological findings analyzed correlated with the presence or absence of EBV. This shows that a definitive diagnosis of HL cannot be established based on histopathological findings alone. Because there are many important implications on the establishment of definitive diagnosis of HL, the detection of EBV by ISH is obligatory.

Oral lesions are common in women and children with HIV/AIDS and may decrease the overall quality of life in these patients because of pain, dry mouth, and difficulty in eating. An oral cavity screening is an easy, noninvasive, quick, and inexpensive procedure that provides nurses with invaluable information about the need for referral, treatment, and health education. Nurses can use the information obtained from a careful oral screening to decrease the symptoms experienced with oral lesions and optimize a patient's ability to chew and enjoy food. Common oral manifestations of HIV infection include fungal, viral, and bacterial infections, although neoplasms, periodontal disease, salivary gland disease, and lesions of uncertain origin are also seen. Oral lesions such as candidiasis, oral hairy leukoplakia, herpetic ulcers, and Kaposi's sarcoma are often among the first symptoms of HIV infection.

The objective of the study is to establish the prevalence of oral manifestations and their influence on oral functions. A total of 514 subjects aged 18 to 58 years (mean 42 years) were randomly recruited from five The AIDS Support Organization (TASO) clinics in Uganda. They were clinically examined for oral lesions under field conditions by four trained dentists based on World Health Organization criteria. Women constituted 74.5% of the study population. Oral manifestations were recorded in 72% of the subjects, out of which 70% had candidiasis of pseudomembranous, erythematous, and angular cheilitis variants. Non-Hodgkin's lymphoma, atypical ulcers, necrotizing periodontitis, and hairy leucoplakia were least frequently observed in the subjects. Of those who had oral lesions (n = 370), 68.4% had some form of discomfort in the mouth. Tooth brushing, chewing, and swallowing were frequently associated with discomfort. Reported forms of discomfort were dry mouth, increased salivation, and burning sensation especially on taking salty and spicy foods or acidic drinks. Only 8.5% (n = 44) of the subjects were taking medications specifically for oral lesions, which included antifungal, antiviral, and antibacterial agents. None of the subjects were on antiretroviral therapy. Oral lesions associated with human immunodeficiency virus/acquired immunodeficiency syndrome in TASO clients is a major public health problem requiring education in recognition and appropriate management.

Epstein-Barr virus (EBV) BMRF-2 protein interaction with the beta1 family of integrins plays an important role in EBV infection of polarized oral epithelial cells. In this work, we characterized BMRF-2 protein expression in EBV-infected B lymphoblastoid and polarized oral epithelial cells, and in hairy leukoplakia (HL) epithelium. BMRF-2 expression in B cells and polarized oral epithelial cells was associated with the EBV lytic infection. In these cells, BMRF-2 is efficiently transported to the cell membrane and its integrin binding Arg-Gly-Asp (RGD) motif is exposed on the cell surface. BMRF-2 is highly expressed in HL epithelium and accumulates at the lateral border of oral keratinocytes. In EBV-infected polarized oral epithelial cells, this protein is transported to the basolateral membranes and co-localized with beta1 integrin. These data suggest that BMRF-2 may play an important role in cell-to-cell spread of EBV within the oral epithelium. BMRF-2 is glycosylated through O-linked oligosaccharides; it forms oligomers and is associated with the virion envelope. Its C-terminal tail is localized in the cytoplasm. We found that beta1, alpha5, and alpha3 integrins are present in purified EBV virions. We show that BMRF-2 is a ligand for beta1, alpha5, alpha3, and alphav integrins and our data are consistent with a role for BMRF-2 in viral lytic infection.

The use of the polymerase chain reaction (PCR) to detect the presence of Epstein-Barr virus (EBV) DNA in oral mucosa in the absence of specific lesions gives rise to the problem of identifying the real viral replication sites. To verify whether the detection of EBV is due to salivary contamination or its true replicative capacity in oral mucosa, saliva samples and exfoliated cells from four different oral mucosa sites were taken from 40 renal transplant patients and 20 normal subjects for examination by PCR using two pairs of primers specific for the BamHI-L and BamHI-K genomic regions. EBV-specific sequences were detected in one or more of the oral mucosa samples from 29 transplant patients (72.5%) and six healthy controls (30%), and in the saliva samples of 16 transplant patients (40%) and three healthy controls (15%). A total of 89 oral mucosa smears from 29 transplant patients, and 13 from healthy subjects, were EBV-positive. The positive samples were also investigated by means of in situ hybridization in order to confirm the intracellular presence of the viral genome, and by means of immunofluorescence testing with monoclonal antibodies to assess the possible expression of viral antigens. Hybridization with the EBV-specific probe was observed in 40/ 89 and 2/13 samples, respectively. Latent antigens (with or without lytic antigens) were detected in only 23 of the 40 samples (collected from eight different transplant patients) that were positive by in situ hybridization. Our data show that EBV is more frequently present in the oral mucosa of immunodeficient patients (where it can efficiently replicate) than in normal subjects.

A cross-sectional analysis was conducted in Mexico City from September 1989 to March 1996, to determine the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The diagnosis of HIV-associated oral lesions was based on preestablished criteria. For the statistical analysis chi-squared and Fisher's exact tests were used where appropriate. Odds ratios were calculated as estimates of the relative risks. Control of confounding factors was performed by logistic regression models. Oral lesions were present in 75% of 436 HIV+ patients. Hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis and oral ulcers were frequently found. Patients who contracted HIV through blood transfusion were more likely to present erythematous candidosis (P=0.005) than subjects who acquired HIV through sexual transmission. Oral ulcers were seen only in men (P=0.02) and in individuals who contracted HIV through sexual transmission (P=0.02). This study brings valuable data in regard to differences in the type and prevalence of HIV-related oral lesions by gender and the risk categories analysed, particularly blood transfusion.A cross-sectional analysis conducted in Mexico City, Mexico, in 1989-96 investigated the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The 436 HIV-positive patients enrolled in this study were part of a larger, ongoing study conducted through the Infectious Diseases Clinic in Mexico City. The primary mode of HIV transmission was blood transfusion among female respondents (63%) and sexual activity among male respondents (90%). 71% of subjects had at least 1 (mean, 1.3) HIV-related oral lesion, including hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis, and oral ulcers. Candidosis, pseudomembranous candidosis, hairy leukoplakia, exfoliative cheilitis, and xerostomia were all significantly associated with a CD4 count under 200 cells/cu. mm and were more prevalent among those with advanced HIV disease. Oral ulcers were present only in men. Women had a higher prevalence than men of hyperpigmentation (10.5% vs. 4%) and xerostomia (7% vs. 2%), but these differences were not significant. Multivariate analysis revealed a significant association between erythematous candidosis and blood transfusion, even after controlling for gender, clinical stage, CD4 count, antiretroviral therapy, smoking history, and xerostomia.

Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse on Oral Problems related to HIV infection and the WHO Collaborating Centre on Oral manifestations of the immunodeficiency virus, were studied in 600 consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%, hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those reported elsewhere, but socio-cultural differences allowed no reliable comparison. More than a quarter of our patients had oral soft tissue discomfort necessitating treatment; in 3.3% these were the presenting symptom. This indicates a potential major public health concern requiring education in recognition and appropriate referral and management.The prevalence and clinical appearance of oral manifestations of HIV were investigated in 600 consecutive HIV patients examined at health care facilities in Cape Town, South Africa, in 1993-96. At least 1 oral lesion was present in 362 patients (60.4%). 160 oral manifestations (26.7%) were symptomatic and required treatment. The majority of lesions (37.8%) were candidosis, primarily pseudomembranous and erythematous types. Oral hairy leukoplakia was present in 19.7% of patients, while HIV-related peridontal disease was noted in 8.5%. 20 HIV-positive patients (3.3%) presented with an oral manifestation of HIV infection before HIV was diagnosed. Classifications were based on guidelines developed by the EC-Clearinghouse on Oral Problems Related to HIV Infection and the World Health Organization Collaborating Center on Oral Manifestations of the Immunodeficiency Virus. These findings, which are similar to those reported in other developed and developing countries, indicate a need for education on the recognition and appropriate management and referral of oral manifestations of HIV infection.