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.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections.

AIMS: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. METHODS AND RESULTS: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)-negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. CONCLUSIONS: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

The advantages of oral cytopathology in the early diagnosis of HIV/AIDS: three case reports.

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.

Iatrogenic oral hairy leukoplakia: report of two cases.

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.

Oral Hairy Leukoplakia in Immunocompetent Patients Revisited with Literature Review.

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.

[Leukoplakia and erythroplakia--two orale precursor lesions]. / Leukoplakie und Erythroplakie--Zwei orale Präkursorläsionen.

The oral leukoplakia/erythroplakia is one of the most common epithelial precursor lesions of the oral squamous cell carcinoma. A clinical distinction is drawn between homogeneous and non-homogeneous as well as proliferative verrucous leukoplakia and erythroplakia. Due to the fact that the oral squamous cell carcinoma has a poor prognosis it is very important to decrease morbidity and mortality by systematic primary, secondary and tertiary prevention of the oral leukoplakia/erythroplakia. On the basis of histological classification systems the risk of malignant transformation can be evaluated, a defined therapy can be induced and the prognosis can be derived.

Targeted therapy of oral hairy leukoplakia with gentian violet.

Oral hairy leukoplakia (OHL) is a common oral manifestation of HIV infection. Clinically, these lesions appear as white plaques on the edges of the tongue. Pathophysiologically, these lesions occur because of infection of oral epithelium with Epstein-Barr virus (EBV). No universally effective therapy exists for OHL. We have previously shown that EBV infection and EBV viral products induce the generation of reactive oxygen. We have also demonstrated that the Food and Drug Administration-approved over-the-counter medication gentian violet is a potent inhibitor of reactive oxygen species. We thus chose to treat a patient with biopsy-proven OHL with topical gentian violet. Gentian violet solution was applied topically to the tongue of a patient with OHL. Complete clinical resolution was noted after three treatments. Treatment with topical gentian violet resulted in resolution of the lesions. Further studies with larger numbers of patients are required. The application of gentian violet can be used as a method to OHL treatment. Gentian violet is an inexpensive and safe therapy and, given that it inhibits reactive oxygen, this old therapy is now a targeted novel therapy.

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.

A non-invasive technique for studying oral epithelial Epstein-Barr virus infection and disease.

Oral Epstein-Barr virus (EBV) infection is associated with hairy leukoplakia and possibly other oral diseases. Many studies of oral EBV infection utilize surgical specimens. This study tested a non-invasive brush biopsy technique as an alternative to surgical biopsy to study oral EBV infection and disease. Paired, same-site, samples of tongue epithelium were obtained from research subjects, first by brush and then by surgical biopsy. Brush cells and surgical specimens were fixed and prepared for histologic sectioning and/or processed for nucleic acid extraction. Brush cell pellet sections proved equivalent to surgical specimen tissue sections for hairy leukoplakia diagnosis by routine histologic staining and EBV immunohistochemistry or in situ hybridization. Amplification of EBV sequences demonstrated superiority of the brush cells over surgical specimens for both sensitivity (90% vs. 73%) and negative predictive value (93% vs. 82%). This non-invasive brush biopsy technique should facilitate larger, prospective studies of oral EBV infection and pathogenesis.

Oral lesions in HIV/AIDS patients undergoing highly active antiretroviral treatment including protease inhibitors: a new face of oral AIDS?

The objective of this work was to assess the prevalence of human immunodeficiency virus-related oral lesions (HIV-ROL) in HIV-positive/acquired immunodeficiency syndrome (AIDS) patients receiving highly active antiretroviral therapy (HAART) including HIV-protease inhibitors. One hundred fifty-five (154) AIDS patients (69 intravenous drug users [IDU], 53 heterosexuals, 29 males who have sex with males, 1 transfused, and 2 of unknown contagious source) receiving HAART, were examined. We found the following prevalences: HIV-ROL 53.2%; oral candidiasis 34.4%; hairy leucoplakia 26.6%; xerostomia 15.5%; herpes simplex labialis 1.9%; HIV/periodontitis-gingivitis 0.6%. No cases of Kaposi's sarcoma were observed. The highest prevalence of HIV-ROL was found in the IDU group, and in patients with viral load more than 10,000 copies and CD4(+) cell count less than 200. Using our historical controls, this suggests that the prevalence of all oral lesions, particularly oral candidiasis, herpes simplex labiali, Kaposi's sarcoma, and periodontal disease has decreased more than 30% after the institution of HAART.

Exfoliative cytology and electron microscopy in the diagnosis of hairy leukoplakia.

The diagnosis of lesions clinically suggestive of hairy leukoplakia was assessed by light and electron microscopic examination of cytologic smears. We found exfoliative cytology to be a simple and noninvasive technique that can confirm the clinical diagnosis of hairy leukoplakia. Our results suggest that electron microscopy may be more sensitive and reliable than light microscopy in confirming the clinical diagnosis of hairy leukoplakia.

Oral manifestations of human immunodeficiency virus (HIV)-infected patients in Singapore.

INTRODUCTION: Oral lesions have been recognised as prominent features of acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection since the beginning of the epidemic. OBJECTIVE: This descriptive study was conducted to study the types of oral lesions among HIV-infected patients in Singapore. MATERIALS AND METHODS: Oral examination was done on 81 randomly selected HIV-infected patients attending the specialist outpatient clinic at the Communicable Disease Centre. RESULTS: A total of 9 different lesions were observed in 45 (56%) patients. The lesions observed were oral candidosis (35%), periodontal disease (16%), aphthous-like ulcers (5%), oral hairy leukoplakia (5%) and lymphoma (1%). CONCLUSION: The oral manifestations of HIV-infected patients in Singapore appear to be less frequent in comparison with those patients from Africa and Europe. Similarities in oral findings among the HIV-infected patients in Asia are evident with a notable lack of oral Kaposi's sarcoma (KS) and a low prevalence of non-Hodgkin's lymphoma and oral hairy leukoplakia.

[Oral hairy leukoplakia: histopathologic features of subclinical stage]. / Leucoplasia pilosa oral: aspectos histopatológicos da fase subclínica.

Oral hairy leukoplakia (OHL) is one of the most common oral manifestations of AIDS, with diagnostic and prognostic value. OHL is associated to the Epstein-Barr virus and presents clinical and histological defined characteristics. There have already been reports about a subclinical stage of OHL, although they lacked histopathologic characterization. The present study had the aim to describe the histopathological characteristics of subclinical hairy leukoplakia, as well as to carry out a comparative analysis between clinical and subclinical OHL. For that, 11 cases were analyzed--5 biopsies from patients who presented with the lesion and 6 samples from the borders of tongues obtained in necropsies. The histopathological findings in subclinical OHL were: absence of parakeratosis and papillomatosis, mild acanthosis, ballooning cells and nuclear alterations. In situ hybridization and immunostaining were positive for EBV in the nuclear alterations identified in the histopathological analysis. Based on the identification of EBV in the nuclear alterations, it was possible to conclude that subclinical OHL, similarly to the clinical lesion, presents histopathological features that are specific and sufficient to establish the definitive diagnosis, regardless of the identification of the virus.

Case report on a rare lesion in an HIV-infected child: hairy leukoplakia.

This report describes a case of hairy leukoplakia in an HIV-infected child, and the treatment adopted. It was diagnosed by clinical and laboratory examinations, using exfoliative cytology (staining by the Papanicolaou method) and additional information was obtained by optical microscope analysis. In view of the lack of painful symptoms, of the innocuous nature of the lesion and large amount of medicines used by the patient, we decided to preserve and monitor the lesion.

Oral hairy leukoplakia in an HIV-negative patient.

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.