Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

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.

EBV Association with Lymphomas and Carcinomas in the Oral Compartment.

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus infecting approximately 90% of the world's population. The oral cavity serves a central role in the life cycle, transmission, and pathogenesis of EBV. Transmitted to a new host via saliva, EBV circulates between cellular compartments within oral lymphoid tissues. Epithelial cells primarily support productive viral replication, while B lymphocytes support viral latency and reactivation. EBV infections are typically asymptomatic and benign; however, the latent virus is associated with multiple lymphomas and carcinomas arising in the oral cavity. EBV association with cancer is complex as histologically similar cancers often test negative for the virus. However, the presence of EBV is associated with distinct features in certain cancers. The intrinsic ability of EBV to immortalize B-lymphocytes, via manipulation of survival and growth signaling, further implicates the virus as an oncogenic cofactor. A distinct mutational profile and burden have been observed in EBV-positive compared to EBV-negative tumors, suggesting that viral infection can drive alternative pathways that converge on oncogenesis. Taken together, EBV is also an important prognostic biomarker that can direct alternative therapeutic approaches. Here, we discuss the prevalence of EBV in oral malignancies and the EBV-dependent mechanisms associated with tumorigenesis.

Physical Examination in Human Immunodeficiency Virus Disease.

Human immunodeficiency virus (HIV)-associated disease is known for its protean manifestations. However, many of the characteristic findings on physical examination are not associated with HIV infection per se but the numerous opportunistic infections (OIs) that are common in patients with advanced HIV disease. Common findings of acute HIV infection include fever, adenopathy, rash, and oral ulcers. Chronic HIV infection is associated with skin, rheumatologic, and neurologic manifestations. OIs also cause skin, oropharyngeal, ocular, and neurologic manifestations. A skilled clinician can often recognize HIV disease based on the combination of these findings.

Onycho-mucocutaneous syndrome secondary to human immunodeficiency virus disease.

Cutaneous, mucosal, and nail examination is the key to unveiling a plethora of systemic diseases. Mucocutaneous lesions directly related to human immunodeficiency virus (HIV) infection usually present as initial manifestations of immune deficiency, of which few lesions act as predictors of an immunocompromised state. Here, we report two cases who presented with onycho-mucocutaneous symptoms which raised the suspicion of and invariably led to the diagnosis of an underlying immunosuppression secondary to HIV infection.

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.

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.

A 45-year-old Female with an Atypical Presentation of Pharyngitis.

INTRODUCTION: Emergency physicians are trained to treat a variety of ailments in the emergency department (ED), some of which are emergent, while others are not. A common complaint seen in the ED is a sore throat. While most sore throats are easily diagnosed and treated, less common causes are often not considered in the differential diagnoses. Therefore, the purpose of this case study was to present an atypical case of sore throat and discuss differential diagnoses. CASE PRESENTATION: The patient was a 45-year-old female who presented to the ED with a three-day history of sore throat that was exacerbated by eating and drinking. The patient was not on any prescription medications, but tried over-the-counter medications for the sore throat without any improvement in symptoms. Review of systems was positive for sore throat, fevers, and chills. Physical examination of her oropharynx revealed mildly dry mucous membranes with confluent plaques and white patchy ulcerative appearance involving the tongue, tonsils, hard palate, and soft palate. Rapid streptococcal antigen, mononucleosis spot test, and KOH test were performed and found to be negative. DISCUSSION: After initial testing was negative, a follow-up complete blood count with differential and complete metabolic profile were ordered. The patient was found to have decreased lymphocytes and platelets. Based upon those results, a diagnosis was made in the ED, the patient was started on medication, and further laboratory workup was ordered to confirm the diagnosis. ED providers should consider non-infectious as well as infectious causes for a sore throat, as this might lead to a diagnosis of an underlying condition.

Oral hairy leukoplakia in a child using a corticosteroid nasal spray.

We report a case of atypical oral hairy leukoplakia (OHL) in a 9-year-old immunocompetent girl treated with fluticasone propionate nasal spray for allergic rhinitis. The OHL in childhood is uncommon and should be included in a differential diagnosis of white lesions in the oral mucosa.

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.

Oral hairy leukoplakia in healthy immunocompetent patients: a small case series.

BACKGROUND: 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. METHODS: 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. CASE REPORT: Four cases of OHL in immunocompetent individuals were identified. All lesions were located on the lateral borders of the tongue. DISCUSSION: 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.

A Case of Secondary Syphilis Presenting as a "Leukoplakia-like" Plaque on the Tongue in a HIV Patient / 대한피부과학회지

"Leukoplakia-like" plaque on the tongue is an uncommon skin manifestation of secondary syphilis. Skin lesions of secondary syphilis usually have numerous presentations, which mimic many other skin diseases, especially in the presence of HIV co-infection. Oral hairy leukoplakia (OHL) is characterized by corrugated whitish patches and plaques on the lateral border of the tongue. It is frequently and strongly associated with HIV but may appear in other diseases. A 47-year-old man with HIV and receiving HAART therapy developed a leukoplakia-like plaque on the tongue, which was first suggestive of OHL but was eventually diagnosed as secondary syphilis.

[Oral hairy leukoplakia induced by topical steroids]. / Leucoplasie orale chevelue induite par une corticothérapie locale.

BACKGROUND: Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. PATIENTS AND METHODS: An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. DISCUSSION AND CONCLUSION: To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa.

Epstein-Barr virus: dermatologic associations and implications: part I. Mucocutaneous manifestations of Epstein-Barr virus and nonmalignant disorders.

Epstein-Barr virus (EBV) is a ubiquitous virus that has been implicated in a wide range of human diseases, many of which have mucocutaneous manifestations. As a member of the herpesviridae family, EBV causes lifelong infection by establishing latency in B lymphocytes. An intact immune response is critical in preventing progression of EBV disease, and the clinical manifestations of infection are dependent on the intricate relationship between virus and host immune system. This review provides a comprehensive overview of the epidemiology, pathophysiology, and diagnostic testing in EBV infection. In part I of this continuing medical education article, the mucocutaneous manifestations of EBV infection are reviewed with an emphasis on pathophysiology and management.

Critical review of topical management of oral hairy leukoplakia.

Oral hairy leukoplakia (OHL) is a disease associated with Epstein-Barr virus and human immunodeficiency virus infections. OHL is usually an asymptomatic lesion, but in some cases treatment is recommended to reestablish the normal characteristics of the tongue, to eliminate pathogenic microorganisms, to improve patient comfort and for cosmetic reasons. Proposed treatments for this condition include surgery, systemic antiviral treatment and topical management. Topical treatment is an inexpensive and safe therapy that is easy to apply, noninvasive, free of systemic adverse effects and effective over a long period of time. The aim of this study was to present a review of the literature for topical therapy for OHL. Gentian violet, retinoids, podophyllin, acyclovir and podophyllin associated with topical antiviral drugs were used to treat OHL. Reports with this focus are limited, and since 2010, no new studies have been published that discuss the efficacy of topical treatments for OHL. Podophyllin with acyclovir cream was found to be effective, causing regression of lesions with no recurrences. Additional searches are necessary to provide clinical evidence of topical management effectiveness.

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 lesions associated with human immunodeficiency virus disease.

Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications.

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.

Oral hairy leukoplakia which occurred as a presenting sign of acute myeloid leukemia in a child.

Oral hairy leukoplakia (OHL) is caused by the reactivation of a previous Epstein-Barr virus (EBV) infection in the epithelium of the tongue. Most lesions are characterized by corrugated whitish patches on the lateral border of the tongue. It is frequently associated with AIDS, but cases in patients with other immunosuppressed states have also been reported. In leukemia patients, OHL is rarely encountered, and appears only after chemotherapy. We report a case of OHL which occurred as a presenting sign of acute myeloid leukemia (AML) in a previously healthy 15-year-old child. A 15-year-old boy presented with a whitish patch on the left lateral border of the tongue. The biopsy specimen revealed papillomatosis, hyperkeratosis, acanthosis and ballooning degeneration in the stratum spinosum. The patient was EBV seropositive, and PCR analysis of EBV DNA in the lesional tissue was positive. After the diagnosis of OHL in dermatologic department, the patient was referred to pediatrics due to the abnormal peripheral blood smear, and was diagnosed with AML.