Hairy leukoplakia: an AIDS-associated opportunistic infection

Hairy leukoplakia has been defined and confirmed as a specific oral mucosal marker for human immunodeficiency virus infection. Light microscopic findings include alteration of spinous layer cells, which contain nuclear chromatin abnormalities. Enlargement of spinous cells with ballooning degeneration is also characteristic. Ultrastructural morphology has defined the presence of large numbers of herpes-type virus particles within the intranuclear, cytoplasmic, and intercellular regions. Morphologically, the criteria of Epstein-Barr virus are satisfied. Southern blot analysis has confirmed the virus to be Epstein-Barr virus. Further hybridization analyses failed to show any evidence of human immunodeficiency virus or human papillomavirus in the lesions themselves. We conclude that hairy leukoplakia may represent an epithelial opportunistic Epstein-Barr virus infection. Finally, the production and shedding of Epstein-Barr virions into the oral cavity from the sites of hairy leukoplakia can occur separate from the usual tonsillar and oropharyngeal sites.     

Diagnosis of oral hairy leukoplakia by ultrastructural examination of exfoliative cytologic specimens

Lingual exfoliative cytologic specimens (scrapings) were obtained from 18 patients positive for human immunodeficiency virus with clinical oral hairy leukoplakia. Buccal mucosal scrapings were obtained from 12 of these patients. The specimens were processed for examination by transmission electron microscopy (TEM). Sixteen (89%) of the lingual specimens revealed infection of keratinocytes by herpes-type virus. There was no evidence of virus infection in the 12 buccal mucosal scrapings. Fungal hyphae were seen by TEM in 14 (78%) of the lingual scrapings and two (17%) of the buccal scrapings. One exfoliative specimen and two biopsy specimens were stained for Epstein-Barr virus DNA with a DNA probe. The demonstration of herpes-type virions by TEM in keratinocytes from a lesion clinically suspected to be hairy leukoplakia provides direct, objective diagnosis. Furthermore, use of exfoliative cytologic specimens provides a clinically simple, noninvasive technique.     

Hairy leukoplakia after bone marrow transplantation

Hairy leukoplakia in 10 patients after bone marrow transplantation was identified clinically and assessed histologically. In situ hybridization for Epstein-Barr virus and human papilloma virus confirmed Epstein-Barr virus in hairy leukoplakia in two cases, and human papillomavirus in three cases. All cases with clinical follow-up resolved without treatment. These findings suggest that severe immunosuppression after a bone marrow transplantation may result in the development of hairy leukoplakia, and that as the immunosuppression resolves after the transplant the lesions also resolve.     

Oral hairy leukoplakia in HIV infection: a diagnostic pitfall.

Twenty-nine human immunodeficiency virus (HIV)-infected patients with white, nonremovable lesions on the lateral border of the tongue, clinically suggestive of oral hairy leukoplakia (HL), were studied. In particular, the value of local antifungal therapy in establishing the diagnosis of HL was investigated. In 15 patients (52%) the lesions could be ultimately attributed to a candidal infection of the tongue. In 10 of the remaining 14 patients, a biopsy was obtained from lesions persisting after local antifungal treatment. In all biopsy specimens, the diagnosis of HL was confirmed by histopathologic examination and the demonstration of Epstein-Barr virus DNA by polymerase chain reaction, Southern blot hybridization, and DNA in situ hybridization. The present data confirm that the diagnosis of HL in HIV-infected patients cannot be reliably made on clinical criteria alone, but requires histopathologic confirmation including the demonstration of Epstein-Barr virus DNA, preferably by DNA in situ hybridization. However, with regard to the differential diagnosis of white, nonremovable lesions on the lateral border of the tongue in HIV-infected patients, the present study suggests that persistence of lesions after local antifungal therapy is highly suggestive of HL.     

Epstein-Barr virus DNA detection in gingival tissues of patients undergoing surgical extractions.

The main oral manifestation of Epstein-Barr virus (EBV) infection is hairy leukoplakia, a lesion associated with the acquired immunodeficiency syndrome (AIDS) and occasionally in other immunocompromised patients. However, the recent literature describes the presence of viral genome in clinically normal oral tissues. The purpose of this work was to investigate these occult EBV infections in gingival epithelium. The Southern blot method with 32P-radiolabelled DNA probes under stringent conditions was applied to 20 interproximal gingival papillae specimens and revealed homologous EBV sequences in 4 of 10 AIDS patients as well as in 4 of 10 HIV negative patients. In order to determine whether EBV has a predilection for the gingival tissues, samples of nasal, laryngeal and oral mucosa, other than gingival mucosa, were collected from 10 HIV-negative patients undergoing surgical treatment for a variety of clinical conditions. None of these extra-periodontal mucosal specimens contained homologous EBV DNAs, except an edentulous palatal gingival specimen. With the present detection of EBV DNAs in the gingival tissues of patients undergoing surgical extractions, it would be of interest to investigate more systematically these subclinical infections in order to determine their exact implications in oral disease.     

Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Clinical results in nine patients.

Hairy leukoplakia was first described as an oral marker of human immunodeficiency virus infection in 1984. The clinical significance of this lesion in an otherwise healthy, high-risk symptom-free person is that it can be an early manifestation of human immunodeficiency virus infection. Because of its benign nature and the lack of clinical evidence that treatment of the lesion improves the prognosis of human immunodeficiency virus-infected patients, systemic therapy with antiviral drugs does not seem warranted at this time. Topical retinoids (Retin-A sol) and systemic antivirals such as acyclovir have been previously tried; however, lesions tend to recur a few days after treatment is discontinued. Nine patients with oral hairy leukoplakia seen at the Oral Medicine Clinic, University of California San Francisco were offered treatment with podophyllum resin 25% sol. All patients had a complete remission of their condition within 1 week (5 patients) or after the second application a week later (4 patients). Side effects were transient and reversible. These remissions of oral hairy leukoplakia lasted from 2 to 28 weeks, which suggests that podophyllum may be a relatively safe and cost-effective treatment of this otherwise symptom-free lesion.     

Oral hairy leukoplakia. Early sign of AIDS

Oral hairy leukoplakia (OHL) is a new lesion that appears specifically on the lateral borders of the tongue. It has basically been detected in immunosuppressed male homosexuals and it is associated with the later development of the acquired immunodeficiency syndrome (AIDS) or HIV infection. Epstein-Barr virus has been suggested to be the possible etiological agent. A review of the existing literature pointing out definition, clinical, histopathologic and ultrastructural features, prognostic and treatment is made. Moreover the characteristics of the individuals suffering from it are equally studied. The role of the dentist at detecting the lesion, as well as the importance of its definitive diagnostic are emphasized, in virtue of the effects that may have a bearing on patients.     

Oral findings in patients with acquired immunodeficiency syndrome

Oral examinations of 103 consecutive patients with acquired immunodeficiency syndrome (AIDS) were performed. Of these patients, 74 (72%) were heterosexuals and 29 (28%) were homosexual or bisexual men. Lesions that were identified on subsequent examination were recorded separately. Oral candidiasis was the most common finding, occurring in 94 patients. Other findings were herpes simplex ulceration (ten patients), exfoliative cheilitis (nine patients), xerostomia (ten patients), "hairy" leukoplakia (seven patients), and Kaposi's sarcoma (four patients). A patchy, depapillated tongue was seen in six patients, and ulcers with uncertain cause were seen in three patients. Gingival bleeding, perioral molluscum contagiosum, and brown hairy tongue each occurred in one patient. In this study, "hairy" leukoplakia and Kaposi's sarcoma occurred exclusively in homosexual and bisexual men with AIDS, and occurred significantly more frequently in this group than in heterosexual patients with AIDS. There was no significant difference between these groups in the frequency of occurrence of other findings.     

Oral hairy leukoplakia: diagnosis and management

Oral hairy leukoplakia (HL) is a remarkable lesion associated with Epstein-Barr virus (EBV) found in persons infected with the human immunodeficiency virus. The clinical and histologic features of HL are characteristic and distinctive. However, none of these features are entirely specific for HL, and we consider that the presence of EBV is required for diagnosis in questionable cases. EBV can be demonstrated by means of electron microscopy, immunocytochemistry, or molecular biologic techniques. Therapy directed toward the HL lesion is sometimes indicated; acyclovir is the current drug of preference in such cases.     

Oral hairy leukoplakia in three hemophiliacs with human immunodeficiency virus infection

Oral manifestations in AIDS, in AIDS-related complex, and in patients with antibodies to the AIDS-causing virus, human immunodeficiency virus (HIV), have been described previously. One of these manifestations, oral hairy leukoplakia, is apparently specifically associated with HIV infection and has until recently been reported in homosexual men only. This article demonstrates, among European patients, the occurrence of hairy leukoplakia in three patients belonging to another risk group for AIDS, namely HIV-infected hemophiliacs.     

Detection of Epstein-Barr virus and human papillomavirus type 16 DNA in hairy leukoplakia by in situ hybridisation and the polymerase chain reaction

Demonstration of Epstein-Barr virus (EBV) is considered desirable for the accurate diagnosis of hairy leukoplakia (HL). Previous studies have reported possible associations with human papillomavirus (HPV) infection although this is not a universal finding. Presence of EBV and HPV 16 was examined in biopsy specimens from 18 cases of HL and ten control specimens by in situ hybridisation using digoxigenin-labellcd synthetic oligonucleotide probes and by the polymerase chain reaction (PCR). The presence of EBV was demonstrated in 12 cases by both techniques. Of the remaining six cases EBV could be detected in three by in situ hybridisation but not by PCR; EBV was not detected by either method in a further three cases. All samples were negative for HPV 16 by both techniques under conditions of high stringency, although when stringency of in situ hybridisation was reduced, four samples appeared to harbour HPV DNA sequences. This study provides further evidence to support the role of EBV in the pathogenesis of HL and suggests that HPV 16 is not regularly encountered.     

Oral hairy leukoplakia is not a specific sign of HIV-infection but related to immunosuppression in general

Oral hairy leukoplakia (HL) has been regarded as an early sign of HIV infection, and its clinical importance related to the poor outcome of the patients has been emphasized. Initially, HL was observed exclusively among male homosexuals, but subsequently demonstrated in all risk groups of HIV infection. The patient described in this article suggests that oral HL is not specific for HIV infection per se, but may be associated with immunosuppression also due to other causes. We describe an HIV-seronegative, heterosexual man suffering from an acute myeloblastic leukemia, who developed clinically and histologically typical HL while on cytostatics. Biopsy showed areas with characteristic ballooning cells, and hyphae of yeasts were demonstrated with PAS-stain. Using the in situ hybridization technique, Epstein-Barr virus (EBV) DNA with high copy numbers was disclosed in the superficial and intermediate cells, whereas human papillomavirus (HPV) DNA (types 6, 11, 16, 18) was not present.     

Incidental oral hairy leukoplakia in immunocompetent persons. A report of two cases.

In this brief article we report on two HIV-negative patients with documented oral hairy leukoplakia who had no known risk factors for HIV infection nor any evidence of other forms of immune suppression. Therefore we conclude that in some instances hairy leukoplakia can represent an isolated and innocuous Epstein-Barr virus infection.     

Crystalline inclusions in epithelial cells of hairy leukoplakia: a new ultrastructural finding

Hairy leukoplakia is often the first manifestation of an HIV infection. In the present study we have investigated the ultrastructural features of hairy leukoplakia in two HIV seropositive male homosexual patients. Ultrastructurally EBV particles were found in the upper prickle and keratinized epithelial cells, whereas papilloma virus particles were not found. Candida albicans were also seen in the keratinized layer. In addition two types of inclusions which have not previously been reported in hairy leukoplakia were commonly seen in the epithelial cells containing the EBV. The first was a crystalline microtubular structure which may take the form of several arrays. The second was an elongated multivesicular structure consisting of membrane-bound rounded vesicles embedded in a background of fine filaments. The vesicles were similar to the empty looking EBV particles and their mean diameter was 100 nm. Further investigations are needed to elucidate the exact nature of these structures and their relationship to the Epstein-Barr virus.     

EBV and HSV infections in a patient who had undergone bone marrow transplantation: oral manifestations and diagnosis by in situ nucleic acid hybridization

The course of infections with herpes simplex virus and Epstein-Barr virus in an immunosuppressed patient who had undergone bone marrow transplantation and had tested seronegative for human immunodeficiency virus is described. The clinical oral manifestations were unusual, as they included hairy leukoplakia-like lesions and extensive mucosal ulceration. Histologic examination disclosed unique features consisting of both lichenoid and viral cytopathic changes. The association of the lesions with both Epstein-Barr virus and herpes simplex virus was confirmed by in situ hybridization histochemistry. The importance of recognition of the symptoms, specific diagnosis by DNA hybridization, and implications for antiviral prophylaxis and therapy are emphasized.     

Oral hairy leukoplakia among HIV-positive intravenous drug abusers: a clinicopathologic and ultrastructural study

During a prospective investigation of oral lesions of 120 consecutive patients positive for human immunodeficiency virus, belonging to the intravenous drug abuser risk group and other risk categories, we observed hairy leukoplakia (HL) in 23 cases (19%). The median age of the patients was 27 years (range, 20 to 50 years). Twenty patients were men and three were women. All but two of the twenty three patients used intravenous drugs for a median period of 6 years (range, 5 to 18 years) and were involved in several episodes of needle sharing. Eight men were also bisexual, one man was homosexual, and one man was hemophiliac and bisexual. Eleven patients had asymptomatic infection, five had lymphadenopathy syndrome, six had AIDS-related complex, and one had acquired immunodeficiency syndrome. In all patients, HL lesions were localized on the lateral borders of the tongue. In twelve patients, the lesion was unilateral, and in eleven patients, it was bilateral. Microscopically, hyperparakeratosis and the presence of koilocytes were observed in all cases. Surface candidiasis could be detected with staining with periodic acid-Schiff in two thirds of the cases. In four cases, electron microscopy showed the presence of intracellular and extracellular hyphae of Candida albicans in the parakeratin layer associated with coccobacilli in the spaces between surface epithelial cells. The spinous layer included koilocytes, which had a clear cytoplasmic matrix, sparse organelles and tonofilaments, and dispersed chromatin. These cells were found to be infected by a herpes-type virus in all cases examined. There was no ultrastructural evidence of human papillomavirus in the nuclei of the epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

HIV感染与牙周疾病相关性的研究进展

艾滋病(AIDS)是由感染人类免疫缺陷病毒(HIV)引起的人体免疫功能缺陷疾病,近年来,与艾滋病相关的慢性疾病的研究引发了学者的广泛关注。人们对与HIV相关的慢性病及其相互关系的研究日益增多。HIV感染后很长一段时间没有明显的临床症状,但多数患者在早期就可能出现各种口腔病损,如白色念珠菌病、口腔毛状白斑、HIV相关性牙周病变、卡波西肉瘤以及非霍奇金淋巴瘤等,其中HIV相关性牙周病变较常见。因此,通过牙周组织检查对艾滋病的早期发现具有重要意义。本文将从HIV感染患者的牙周病变表现以及艾滋病与牙周病变发展的关系予以综述。     

Crystalline inclusions in epithelial cells of hairy leukoplakia: a new ultrastructural finding

Abstract – Hairy leukoplakia is often the first manifestation of an HIV infection. In the present study we have investigated the ultrastractural features of hairy leukoplakia in two HIV seropositive male homosexual patients. Ultrastructurally EBV particles were found in the upper prickle and keratinized epithelial cells, whereas papilloma virus particles were not found. Candida albicans were also seen in the keratinized layer. In addition two types of inclusions which have not previously been reported in hairy leukoplakia were commonly seen in the epithelial cells containing the EBV. The first was a crystalline microtubular structure which may take the form of several arrays. The second was an elongated multivesicular structure consisting of membrane-bound rounded vesicles embedded in a background of fine filaments. The vesicles were similar to the empty looking EBV particles and their mean diameter was 100 nm. Further investigations are needed to elucidate the exact nature of these structures and their relationship to the Epstein-Barr virus.     

Prevalence of Epstein-Barr virus and human papillomavirus in oral mucosa of HIV-Infected patients

Epstein-Barr virus (EBV) has been implicated in the genesis of oral hairy leukoplakia (OHL). Initially, OHL was also associated with human papillomavirus (HPV) as evidenced by staining with antiserum to papillomavirus common structural antigens and reports of two HPV-positive OHL as detected by in situ DNA hybridization. The aims of this study were to determine the prevalence of EBV and HPV DNA in OHL and normal oral mucosa and to explain the basis for the staining of OHL tissues with antibodies to papillomavirus common structural antigens. EBV DNA was detected by in situ hybridization in 47 of 47 cases of OHL from human immunodeficiency virus (HIV)-seropositive individuals and in 1 of 10 biopsies of clinically normal buccal mucosa from the same group of individuals. Twenty-five of 35 OHL specimens stained with antibody to papillomavirus common structural antigens. There was no staining of two EBV-containing lymphoblastoid lines, indicating that the staining with anti-papillomavirus antibody was not due to antigenic cross-reactivity with EBV antigens. HPV DNA was detected by polymerase chain reaction amplification in 10 of 18 OHL specimens and in 6 of 10 normal buccal mucosa specimens. Our results indicate that EBV and HPV are present frequently in OHL and that HPV can be found regularly in histologically normal mucosa.