Immunocytochemical detection of herpes viruses in oral smears of HIV-infected patients

Cytologic smears (CS) were taken from the lateral border of the tongue of HIV-seropositive patients (HIV+) (n = 39) and of seronegative controls (HIV-) (n = 19) and examined by immunocytochemistry (APAAP) and in situ hybridization (ISH) (biotinylated DNA probes) for the presence of viral antigens/DNA of EBV and CMV. While none of the HIV controls showed positive results for EBV antigen, 61% (APAAP) resp. 79% (ISH) of oral epithelial cells in the group of HIV+ patients were EBV-positive. While all CS taken from areas with the clinical diagnosis of hairy leukoplakia (HL) were EBV positive (APAAP and/or ISH), the detection of EBV in CS from uninvolved oral mucosa seemed to be associated with the later development of HL. In the group of HIV+ patients the detection rate for CMV was about five times (APAAP) resp. three times (ISH) higher than in HIV- persons. This non-invasive technique seems to be a valuable tool to screen for viral antigens/genomes.     

Cytomegalovirus: a virus of increasing relevance to oral medicine and pathology

Human Cytomegalovirus (H cmv ) is a ubiquitous herpesvirus, emerging as an opportunistic pathogen in immunocompromised persons, particularly those infected with human immunodeficiency viruses (HIV). Clinical syndromes caused by H cmv are usually not specifically identifiable without laboratory investigations. However, it is now apparent that H cmv may cause oral ulceration in immunocompromised persons and it may play a role in other diverse conditions in these and other patients.     

Ultrastructural findings in oral hyperpigmentation of HIV-infected patients

Oral hyperpigmentation has been observed in six HIV-infected patients, in two of whom systemic medication (ketokonazole, clofazimine) was supposed to be etiologically involved. Histologically, pigment was found in epithelial basal cells and particularly in subepithelial connective tissue. Ultrastructurally, the presence of premature melanosomes in subepithelial keratinocytes was of interest. Stimulation of melanocytes during HIV infection may occur in association with immunopathologic changes in the oral mucosa.     

Oral ulcerations in HIV infection

Oral ulceration in HIV infection may be due to: (1) mycotic; (2) bacterial, protozoan; (3) and viral infections; (4) oral neoplasia; (5) aphthous ulceration/ulceration not otherwise specified (NOS); or (6) ulceration of iatrogenic origin. Of particular significance are oral ulcerations caused by viruses of the herpes virus group (HSV 1/2, CMV, VZV) and ulcerations of the aphthous type. It was shown recently that coinfection of viral ulcers occurs. The aetiopathogenesis of the aphthous type of ulcerations including the still debated ulceration NOS is not clear. Further basic and clinical research is necessary in order to better understand ulceration particularly in relation to immunoregulation, tissue breakdown and repair.     

Presence of human herpes virus-8 in saliva and non-lesional oral mucosa in HIV-infected and oncologic immunocompromised patients

BACKGROUND/AIM: Human Herpes Virus-8 (HHV-8) is a recently identified virus etiologically associated with Kaposi's sarcoma. Studies regarding its presence in the oral cavity have given variable results. This study attempted to determine the oral presence of HHV-8 in an area where classic Kaposi's sarcoma is primarily found such as Greece. METHODS: Three groups of patients were studied: 10 immunocompromised with hematologic malignancies, 10 immunocompromised with HIV infection and 20 immunocompetent as controls. Whole unstimulated saliva and scrapes from the lingual and the buccal mucosa were collected and polymerase chain reaction was applied to amplify HHV-8 DNA. RESULTS: None of the patients in any group had oral lesions. In the control group, all samples tested negative (0/60). HHV-8 DNA was detected in 5/30 (17%) of all samples from HIV-positive patients (the mean value of their CD4+ T-lymphocytes being 385/mm3) and in 13/30 (43%) of all samples from oncologic patients (mean CD4+ T-lymphocytes 51/mm3). HHV-8 DNA was found in 10% of saliva samples and 40% of lingual and buccal scrapes both of HIV-infected and of oncologic patients. CONCLUSION: HHV-8 is present in the saliva and the non-lesional oral mucosa (not simultaneously) of patients with impaired immunity, with or without HIV co-infection. The oral epithelium seems to represent an independent location of viral residency and may be of viral replication; the clinical implications need further clarification.     

Severe oral ulceration in patients with HIV infection: A case series

OBJECTIVE: Oral ulceration occurs in an estimated 2–4% of patients with HIV infection. This retrospective observational study describes the aetiology and characteristics of 94 HIV-positive patients with either severe and/or recurrent oral ulceration presenting at a dedicated HIV dental unit over a 4-year period. METHODS: Case records were reviewed for diagnosis investigations, CD4 count, CDC stage and treatment modality. RESULTS: Of the 94 patients 50% had an AIDS diagnosis. In patients with asymptomatic HIV disease minor recurrent oral ulceration was the commonest diagnosis whilst large non-specific neutropenic ulcers were more frequently seen in patients with symptomatic disease with low CD4 counts. A variety of treatment modalities were used including thalidomide. An algorithm is presented for the management of patients with severe oral ulceration.     

Oral and dental care and treatment protocols for the management of HIV-infected patients

This paper describes the workings of the workshop dedicated to oral and dental care and treatment protocols for the management of HIV-infected patients. The questions addressed were: 1) What are the current ethical issues in dental care of HIV patients, do they need to be addressed? 2) Do we need to modify the dental care we give HIV-positive patients? 3) When is it necessary to give antibiotic prophylaxis to HIV-positive patients? 4) What is the evidence for the effective treatment of oral lesions associated with HIV? 5) What is the most successful palliative treatment for KS? 6) Can we provide clinical treatment that has a scientific basis rather being trial based? 7) Is ddI + hydroxy-urea an effective African alternative to HAART? 8) What is the influence of protease inhibitors and HAART on the excretion of HIV in saliva? 9) What is the effect of anti-HIV therapy on the oral mucosa and oral health? This workshop did not fully cover the issue of ddI and hydroxy-urea as an alternative HIV therapy as this was considered to be the remit of general physicians caring for patients with HIV and AIDS rather than that of oral health care workers.     

T-lymphocyte subsets in oral mucosa of patients with recurrent aphthous ulceration

In the present study, the proportion of mononuclear cells and percentages of CD4+ (OKT4+) and CD8+ (OKT8+) were determined in clinically healthy buccal mucosa in patients with recurrent minor aphthous ulceration (RAU) (n = 43) during active and inactive disease as compared with RAU-free controls (n = 15). In lamina propria, the total number of mononuclear cells and subset percentages were determined histologically and immunohistochemically. Mononuclear cell counts in patient specimens were significantly lower than in the control group. CD4+ percentages were not significantly different between controls and patients. CD8+ percentages of the patients were significantly increased during active RAU, but not during inactive RAU as compared with controls. In proportion to the total number of mononuclear cells, CD4+ and CD8+ cell counts per 0.25 mm2 were significantly lower in the patients during both active and inactive disease as compared with controls. Thus, RAU seems characterized by reduced numbers of mononuclear cells, including T-lymphocytopenia in the oral mucosa as such, features that appear more pronounced during active disease than during quiescence.     

Oral mucosal ulceration due to cytomegalovirus associated with human immunodeficiency virus infection. Case report and brief review

Reports of oral lesions associated with cytomegalovirus (CMV) infection in human immunodeficiency virus (HIV) infected patients are uncommon¹. In this article a case of CMV infection associated with oral mucosal ulceration and a brief review of the subject is presented. Establishing the cause of ulceration is important in determining a definitive diagnosis and prescribing appropriate therapy. It is important to recognize that CMV associated oral mucosal ulceration may be the initial manifestation of human immunodeficiency virus (HIV) infection.     

Oral infections due to Cytomegalovirus in immunocompromised patients

Herpes group virus infections in the immunocompromised host are associated with significant morbidity and mortality. Herpes simplex virus (HSV) and to a lesser extent varicella zoster virus (VZV) have long been recognized as causes of oral and peri-oral lesions in subjects undergoing bone marrow transplantation and in individuals infected with the Human Immunodeficiency Virus (HIV). A role for Cytomegalovirus (CMV) in such lesions is less clear and not well documented. This report describes two bone marrow transplant recipients and one individual infected with HIV in whom CMV was implicated as the cause of oral lesions. Diagnostic and management issues as well as clinical implications are discussed.     

Complications in HIV-infected and non-HIV-infected haemophiliacs and other patients after oral surgery

Dental extractions and other oral surgical procedures, including local analgesic injections, potentially can cause problems in haemophiliac and HIV infected persons. There are few data on treatment results in HIV-infected haemophiliacs compared with non-HIV-infected haemophiliacs. The oral surgery treatment results in 48 patients with special needs, including HIV-infected haemophiliacs, non-HIV-infected haemophiliacs, HIV-infected non-haemophiliacs, and a group with other medical problems were therefore studied. Around 20% of the haemophiliacs developed post-oral surgical complications, which was not significantly different whether or not they were HIV-infected. However, complications were less frequent (8%) in HIV-infected non-haemophiliacs or other patients with special needs. Although the patient groups are not large, it would appear that haemophiliacs had more postoperative complications but that the presence of HIV infection had no notable influence on treatment outcome.     

Prognostic value of oral candidosis and hairy leukoplakia in 111 Mexican HIV-infected patients

A follow-up study was carried out to evaluate the prognostic value of hairy leukoplakia (HL) and oral candidosis (OC) in a cohort of 111 asymptomatic Mexican HIV infected patients. Oral exams were performed at baseline and every 6 months, from September 1989 to March 1994. Chi-square contingency table test, the Kruskall-Wallis one-way analysis of variance, the Kaplan-Meier product-limit method and the log rank test were used for the analysis. Univariate and multivariate Cox's proportional hazards analysis were also performed. Fifty-four patients (51%) progressed to AIDS (initially 36 CDC-II and 18 CDC-III). Individuals with HL and/or OC, showed faster development to AIDS than subjects without lesions or other HIV-related manifestations (P=0.008). The presence of OC, HL or both always remained significant despite adjustment for total lymphocytes, CDC stage, zidovudine therapy or its combinations. Oral lesions in HIV infection may be regarded with other clinical and laboratory studies as markers of HIV disease progression and as indicators to begin antiretroviral treatment.     

Ultrastructural findings in clinically uninvolved oral mucosa of patients with HIV infection

Twelve biopsies of clinically normal oral mucosa taken from HIV seropositive patients have been investigated by means of light- and electron microscopy. Vascular abnormalities were found in all biopsies, regardless of the clinical stage of the HIV infection. In particular slit-like vascular channels, sparseness of intercellular junctions and swollen, protruded endothelial cells with an increased quantity of Weibel-Palade bodies were noticed. These findings were similar to those described in lesions of early stage Kaposi's sarcoma.     

Cytomegalovirus (CMV) and Helicobacter pylori(HP) found in oral mucosal ulcers

The possible involvement of Cytomegalovirus (CMV) and Helicobacter pylori (HP) in oral mucosal ulcers is suggested by their role in the development of ulceration at other mucosal sites of the gastrointestinal tract. A series of 29 incisional biopsies from 29 consecutive and apparently immunocompetent patients attending the clinic for oral ulceration were examined by routine histopathology as well as by in situ hybridisation (ISH) with biotinylated CMV and HP DNA probes. In 14/29 biopsies, Giemsa staining disclosed spiral bacteria. Six (20.7%) of these 14 Giemsa-positive samples showed HP DNA on ISH and 3 ulcers (10.3%) contained CMV DNA. In none of the specimens were CMV and HP detected simultaneously. Two of the ulcers containing CMV DNA were found on the labial mucosa and one on the posterior palatal mucosa, whereas all HP DNA-positive ulcers were located on the buccal mucosa. The results indicate that CMV and HP DNA can be found in separate oral mucosal ulcers in apparently immunocompetent adults.     

The prevalence of oral candidiasis in HIV-infected individuals and dental attenders in Edinburgh

This study prospectively assessed the prevalence of oral candidal carriage and oral candidiasis in known HIV-seropositive individuals (n = 121) and other dental attenders in Edinburgh (n = 614). Candida species were isolated from 57.4% of dental attenders and 93.4% of HIV-seropositive subjects. Clinical evidence of oral candidiasis was observed in 6% and 52%) of these groups respectively, erythema-tous forms of candidiasis being the commonest in both groups.     

Fluconazole resistant oral candidiasis in HIV-infected patients

OBJECTIVE: To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. METHODS: Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. RESULTS: Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P< 0.001); and (4) low number of TCD4⁺ cells (<50 mm³, P = 0.002). According to multivariate analysis, previous therapy with fluconazole was the only risk factor that independently influenced the development of Candida spp. resistance (P = 0.003). CONCLUSIONS: The prophylaxis and therapy of mild fungal infections in HIV-infected patients, which may lead to azole resistance, should be carefully considered.     

Changes in oral cytokeratin expression in HIV-infected subjects with long-term use of HAART

Oral Diseases (2012) 18 , 793–801 Objectives: The objectives of this study were to determine (i) the expression of oral cytokeratins (CKs) among human immunodeficiency virus (HIV)‐infected subjects compared with non‐HIV controls, (ii) the oral CK expression in the subjects with highly active antiretroviral therapy (HAART) compared with those without HAART, and (iii) factors associated with the expression of oral CKs. Materials and methods: Oral tissues from buccal mucosa were obtained by punched biopsy in HIV‐infected subjects with and without HAART, and non‐HIV individuals. The samples were processed for immunohistochemical studies of CK1, CK13, CK14, CK16, and involucrin. The staining intensity was scored and recorded. Logistic regression analysis and multi‐way ANOVA test were performed. Results: The expression of CK13, CK14, and CK16 was found to be significantly different between HIV‐infected subjects and non‐HIV individuals (P < 0.05). The expression of those CKs was also significantly different between those who were and were not on HAART (P < 0.05). No significant difference between the groups was observed regarding CK1 and involucrin. Conclusions: Oral epithelial cell differentiation as marked by the CK expression is affected by HIV infection and use of HAART. CKs may be the useful biomarkers to identify HIV‐infected subjects who are at risk of malignant transformation of the oral mucosa because of HIV infection and HAART.     

Risk factors for oral hairy leukoplakia in HIV-infected adults of Brazil

BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL.