Epstein-Barr virus oral shedding and viremia and their association with oral hairy leukoplakia in HIV+ individuals.

OBJECTIVE: To assess the oral shedding and viremia of Epstein-Barr virus (EBV) in HIV-positive patients and their relationship with oral hairy leukoplakia (OHL). METHODOLOGY: A total of 94 HIV-positive patients were included in the study, in which blood and saliva samples were collected for EBV quantification. Data on gender, age, time of HIV seropositivity, combined antiretroviral therapy (cART), CD4+ T-cell counts, and HIV viral load were collected. OHL diagnosis was based on histopathological examination and EBV in situ hybridization. RESULTS: The EBV load in the 94 HIV-positive patients was higher in saliva than in blood (2.4 and 1.6, respectively), and there was a positive correlation between EBV oral shedding and viremia (p = 0.001). Twenty (21.27%) patients had OHL and also a higher EBV load in saliva (mean log10  = 3.11) compared to those who had no OHL (p = 0.045). Presence of OHL was only associated with age (p = 0.030). CONCLUSION: In HIV-positive patients, the presence of OHL was associated with EBV oral shedding but not with viremia, regardless of the amount of circulating CD4+ T cells.

Detection of Epstein-Barr virus DNA in saliva of HIV-1-infected individuals with oral hairy leukoplakia.

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-naïve patients at any CD4 + count.

Oral manifestations of HIV: Can they be an indicator of disease severity? (A systematic review).

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.

Racial differences in dermatologic conditions associated with HIV: A cross-sectional study of 4679 patients in an urban tertiary care center.

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.

Considerations in the diagnosis of oral hairy leukoplakia-an institutional experience.

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.

Oral hairy leukoplakia arising in a patient with hairy cell leukaemia: the first reported case.

Oral hairy leukoplakia (OHL) is an oral mucosal lesion that is associated with Epstein-Barr virus infection. It commonly presents as an asymptomatic, non-removable white patch on the lateral borders of the tongue in individuals who are immunocompromised. Historically, OHL was thought to be pathognomonic of HIV infection; however, it is now an established phenomenon in a range of conditions affecting immune competence. Hairy cell leukaemia (HCL) is a rare chronic B cell lymphoproliferative disease named after the distinctive cytology of the atypical cells. We report the first case of OHL arising in an individual with HCL that resolved following remission of the haematological malignancy.

Oral lesions as an important marker for HIV progression.

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.

Diseases of the tongue.

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).

Hairy leukoplakia; lessons learned: 30-plus years.

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 in patients without HIV: presentation of 2 new cases.

OBJECTIVE: We report 2 cases of oral hairy leukoplakia (OHL) in patients without HIV and present a comprehensive review of OHL in HIV-negative individuals. STUDY DESIGN: Two cases of non-HIV-associated OHL are described. A PubMed search identified previously reported cases. The attributes of those cases were ascertained. RESULTS: OHL was confirmed in both of our cases. Both patients used inhaled steroids for pulmonary disorders, and were found to have depressed levels of immunoglobulin M. Additionally, 76 cases were identified in the literature. The condition occurred in association with various medical conditions, with the majority of patients on immunosuppressant medications (67 of 76). Systemic drugs were implicated most frequently. The condition has also been reported in healthy individuals (6 of 76). CONCLUSIONS: Although thought of as an HIV/AIDS-associated condition, OHL can develop in patients without HIV, including healthy individuals. There is a strong correlation between the use of immunosuppressants and development of OHL in these patients.

Oral hairy leukoplakia in healthy, immunocompetent individuals.

Oral hairy leukoplakia (OHL), while typically associated with HIV infection and immunosuppression, is rarely seen in HIV negative immunocompetent individuals. We report on two cases of OHL in immunocompetent patients.

Knowledge, attitudes and practices of oral health care workers in Lesotho regarding the management of patients with oral manifestations of HIV/AIDS.

Lesotho has the third highest prevalence of HIV in the world with an estimated 23% of the adult population infected. At least 70% of people living with HIV/AIDS (PLWHA) have presented with oral manifestation of HIV as the first sign of the disease. Oral health workers regularly encounter patients presenting with oral lesions associated with HIV disease and therefore need to have adequate knowledge of these conditions for diagnosis and management. The aim of the present study was to determine the knowledge, attitudes and practices of oral health care workers (OHCW) of Lesotho regarding the management of oral manifestations of HIV/AIDS. A descriptive cross-sectional survey was conducted on all 46 OHCW in 26 public and private care facilities in all ten districts of Lesotho. A self-administered questionnaire was used to gather information. The response rate was 100%. Nearly all (94.7%) agreed that oral lesions are common in people living with HIV and/or AIDS. The majority (91.3%) named oral candidiasis (OC) as the most common lesion found in PLWHA while Kaposi's Sarcoma (KS) (34.7%) and Oral Hairy Leukoplakia (OHL) (32.6%) were mentioned as the least common oral lesions of HIV. Most correctly identified the images of oral candidiasis (97.8%), angular cheilitis (86.9%) and herpes zoster (80.4%). Only 16.7% felt they had comprehensive knowledge of oral HIV lesions, although 84.8% reported having previously received training. Almost three quarters (71%) reported that there was no need to treat HIV positive patients differently from HIV negative patients. OHCW in Lesotho demonstrated high confidence levels in their competence in managing dental patients with oral lesions associated with HIV, however, they lacked an in-depth knowledge in this regard. Amongst this group there is a need for comprehensive training with regards to diagnosis and management of oral lesions of HIV including the training of other cadres of health care workers together with nurses and community health workers.

Oral hairy leukoplakia diagnosis by Epstein-Barr virus in situ hybridization in liquid-based cytology.

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.