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.

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.

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.

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.

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 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.

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.

Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!

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.

Oral mucosal status and salivary IgA levels of HIV-infected children.

BACKGROUND: Pediatric HIV is a major world health problem, which is progressing at an alarming rate. Lesions in the mouth and in other tissues and organs (oral and systemic lesions) in pediatric HIV infection are diverse and show differences in clinical presentation and severity from that of adults. Very little data exist for oral lesions in pediatric population in India. To assess oral mucosal status of HIV-infected children and to correlate it with their salivary IgA levels. METHODS: The study group consisted of 150 HIV-infected children aged 6-18 years. They were divided into two groups. Group 1: Children prior to anti-retroviral therapy, Group 2: Children undergoing anti-retroviral therapy (for not more than 3 years). Criteria given by Ramos-Gomez for diagnosis of oral lesions commonly associated with HIV infection in children were used to record the oral lesions. Salivary IgA levels were determined by enzyme-linked immunosorbent assay. Data obtained were subjected to statistical analysis. RESULTS: There was a significant difference in mean secretory IgA (SIgA) levels between the groups (P ≤ 0.05). All the children had one or more oral mucosal lesions, with angular cheilitis being the most common lesion. There was a significant inverse relation between SIgA levels and individual oral mucosal lesions (P ≤ 0.05). The number of oral lesions was inversely related to the SIgA levels. CONCLUSION: Oral mucosal lesions were a significant feature of HIV-infected infection, particularly in children prior to the onset of anti-retroviral therapy. All children showed low SIgA levels. Early recognition and management of oral conditions are important to improve the quality of life in these children.

Urban legends series: oral manifestations of HIV infection.

Human immunodeficiency virus-related oral lesions (HIV-OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV-OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy-to-use diagnostic techniques have been recently introduced likely restricting the importance of HIV-OLs in diagnosis. (iii) The 1993 EC-Clearinghouse classification of HIV-OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV-OL case definitions were updated in 2009 to facilitate the accuracy of HIV-OL diagnoses by non-dental healthcare workers in large-scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV-OLs has been reported for OC and OHL.

Common tongue conditions in primary care.

Although easily examined, abnormalities of the tongue can present a diagnostic and therapeutic dilemma for physicians. Recognition and diagnosis require a thorough history, including onset and duration, antecedent symptoms, and tobacco and alcohol use. Examination of tongue morphology and a careful assessment for lymphadenopathy are also important. Geographic tongue, fissured tongue, and hairy tongue are the most common tongue problems and do not require treatment. Median rhomboid glossitis is usually associated with a candidal infection and responds to topical antifungals. Atrophic glossitis is often linked to an underlying nutritional deficiency of iron, folic acid, vitamin B12, riboflavin, or niacin and resolves with correction of the underlying condition. Oral hairy leukoplakia, which can be a marker for underlying immunodeficiency, is caused by the Epstein-Barr virus and is treated with oral antivirals. Tongue growths usually require biopsy to differentiate benign lesions (e.g., granular cell tumors, fibromas, lymphoepithelial cysts) from premalignant leukoplakia or squamous cell carcinoma. Burning mouth syndrome often involves the tongue and has responded to treatment with alpha-lipoic acid, clonazepam, and cognitive behavior therapy in controlled trials. Several trials have also confirmed the effectiveness of surgical division of tongue-tie (ankyloglossia), in the context of optimizing the success of breastfeeding compared with education alone. Tongue lesions of unclear etiology may require biopsy or referral to an oral and maxillofacial surgeon, head and neck surgeon, or a dentist experienced in oral pathology.

[Progress on study on oral lesions in patients with AIDS].

A large number of studies showed that hairy leukoplakia, pseudomembranous candidiasis, Kaposi' sarcoma, non-Hodgkin's lymphoma, linear gingival erythema, necrotizing ulcerative periodontitis and necrotizing ulcerative gingivitis were the most common lesions in patients with HIV infection and AIDS, and their higher prevalence and incidence rates correlated with the falling CD4 counts and higher virus load of the patients. The use of highly active antiretroviral therapy (HAART) was associated with decreases in the prevalence of oral diseases. Oral manifestations may represent early signs of AIDS disease and call attention to disease progression. Oral fluid has been shown to possess superior sensitivity for HIV antibody detection as serum.

Identification of oral candidosis, hairy leukoplakia and recurrent oral ulcers as distinct cases of immune reconstitution inflammatory syndrome.

Oral lesions such as candidosis, hairy leukoplakia (HL) and oral ulcers are strikingly absent in the numerous reports of immune reconstitution inflammatory syndrome (IRIS). To document oral manifestations attributable to immune reconstitution, we conducted a longitudinal follow-up of a cohort of HIV+ individuals starting highly active antiretroviral therapy (HAART) and completing oral pathology follow-up up to 12 weeks after treatment initiation. HIV-infected patients had oral examinations, CD4+ T-cell count and viral load determinations performed at baseline, and at weeks 4, 8 and 12 after HAART initiation. Among individuals with satisfactory viral response and recovery of > or =50 CD4+ T-cell/microL, eight patients complied with strict IRIS criteria: two developed clinical signs of oral candidosis (OC), two oral ulcers, three HL and one Kaposi's sarcoma. CD4+ T-cell counts at symptom onset suggested no remaining immune suppression. Our findings show that cases of OC, HL and recurrent ulcers can be instances of IRIS.