Intraoral cytomegalovirus lesion and HIV-associated periodontitis in a patient with acquired immunodeficiency syndrome.

Exposure to cytomegalovirus (CMV) is common in persons infected with the human immunodeficiency virus. Autopsy studies have documented the presence of CMV in multiple organs, but CMV is seldom indicated as the causative agent in specific diseases. Few reports have described localized CMV infection in the oral cavity. This may be due to the occult histopathologic appearance during oral mucosal CMV infections and to a lack of awareness of CMV infection as a potential etiologic agent in nonspecific oral ulcerations and other oral disease entities. This report describes an intraoral ulceration with documented presence of a localized CMV infection in association with human immunodeficiency virus-associated periodontitis in a patient with acquired immunodeficiency syndrome. A causative relationship between these two entities, however, cannot be established or excluded.     

与人类免疫缺陷病毒感染和艾滋病相关的口腔疾病的研究进展

艾滋病（AIDS）在口腔的表现是艾滋病诊断的重要指标之一。多数人类免疫缺陷病毒（HIV）感染患者都有口腔表现，但口腔表现却往往被忽视。目前与HIV感染密切相关的主要口腔疾病有口腔黏膜病、牙周病、涎腺疾病及龋病等。本文对HIV感染和艾滋病相关的口腔疾病的研究进展作一综述。     

Cytomegalovirus infection presenting as acute periodontal infection in a patient infected with the human immunodeficiency virus

Abstract During childhood, many people acquire primary infection with Cytomegalovirus (CMV), one of the herpes viruses. If they later become immunosuppressed, such as occurs with human immunodeficiency virus (HIV) infection, CMV is likely to become reactivated. Severe disease caused by CMV is. life-threatening in the HIV-infected population, CMV retinitis, gastritis, colitis, pneumonia, encephalitis and hepatitis have all been reported, but oral lesions due to infection with CMV are rarely reported. We report a case of oral CMV infection which at first was clinically indistinguishable from HIV-associated periodontal disease.     

HIV/TB co-infection: literature review and report of multiple tuberculosis oral ulcers.

Human immunodeficiency virus/tuberculosis (HIV/TB) co-infected subjects demonstrate enhanced HIV replication and plasma viremia; CD4+ T-cell depletion; morbidity and mortality; and susceptibility to secondary bacterial and fungal infections compared to subjects solely infected with HIV. As the incidence of HIV/TB infection has been increasing, one would have expected to encounter oral lesions of tuberculosis more frequently. However, such oral lesions are uncommon. The lesions usually occur as ulcerations of the tongue. We report an additional case in an HIV/TB co-infected 39 year-old black male, who presented with chronic, painless, multiple oral ulcers, occurring simultaneously on the tongue, bilaterally on the palate and mucosa of the alveolar ridge. Microscopic examination confirmed the presence of chronic necrotizing granulomatous inflammation, with the identification of acid fast bacilli in the affected oral mucosal tissue. Anti-retroviral and anti-tuberculous treatment resulted in the resolution of the oral lesions. Confirmatory histopathological diagnosis following a biopsy is essential to determine the exact nature of chronic oral ulceration in an HIV individual and especially to distinguish between oral squamous cell carcimoma, lymphoma, infection (bacterial or fungal) and non-specific or aphthous type ulceration.     

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.     

Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren's syndrome but decreased by HIV infection

Calprotectin levels were determined in whole saliva from patients predisposed to oral candidiasis due to HIV infection or Sj?gren's syndrome and from patients with candidiasis associated with various oral disorders (e.g. lichen planus, oral ulceration). Mean calprotectin levels were higher in whole saliva (2 microgram/ml) than in parotid saliva (0.3 microgram/ml). Oral candidiasis was associated with raised whole saliva calprotectin levels in all groups studied. HIV infection was associated with lower levels of salivary calprotectin, in the presence of high or low salivary Candida counts, although CD4+ lymphocyte counts did not significantly correlate with calprotectin concentrations. Calprotectin levels were elevated in saliva from Sj?gren's syndrome patients with oral candidiasis, consistent with mucosal transudation of calprotectin from inflamed mucosa and limited dilution due to decreased salivary flow rates. This study indicates that oral candidiasis is associated with raised calprotectin levels secondary to mucosal inflammation, but that diminution of this candidacidal factor due to HIV infection may be a predisposing factor in the aetiology of oral candidiasis.     

口腔艾滋病的临床及研究进展

目的 被誉为世纪恶魔的艾滋病正在全球肆虐。根据国家最新资料,我国于1985年首次发现艾滋病病人。截止今年6月底,全国累计报告艾滋病病毒感染者26085例,其中艾滋病病人1111例,死亡584例。据专家估计,至2000年底,全国实际艾滋病病毒感染者已超过60万人,这不能不引起广大医务工作者,包括口腔医务工作者的高度警惕和重视。本文介绍了与艾滋病毒感染有关的主要口腔粘膜损害、交叉感染途径及治疗原则,旨在帮助口腔医务工作者对艾滋病的临床及研究进展有一个正确的认识。     

Human immunodeficiency virus interaction with oral and genital mucosal epithelia may lead to epithelial–mesenchymal transition and sequestration of virions in the endosomal compartments

Oral and genital mucosal epithelia are multistratified epithelial barriers with well‐developed tight and adherens junctions. These barriers serve as the first line of defense against many pathogens, including human immunodeficiency virus (HIV). HIV interaction with the surface of mucosal epithelial cells, however, may activate transforming growth factor‐beta (TGF‐β) and mitogen‐activated protein kinase signaling pathways. When activated, these pathways may lead to the disruption of epithelial junctions and epithelial–mesenchymal transition (EMT). HIV‐induced impairment of the mucosal barrier may facilitate the spread of pathogenic viral, bacterial, fungal, and other infectious agents. HIV‐induced EMT promotes highly motile/migratory cells. In oral and genital mucosa, if EMT occurs within a human papillomavirus (HPV)‐infected premalignant or malignant cell environment, the HPV‐associated neoplastic process could be accelerated by promoting viral invasion of malignant cells. HIV also internalizes into oral and genital mucosal epithelial cells. The majority (90%) of internalized virions do not cross the epithelium, but are retained in endosomal compartments for several days. These sequestered virions are infectious. Upon interaction with activated peripheral blood mononuclear cells and CD4+ T lymphocytes, epithelial cells containing the virus can be transferred. The induction of HIV‐1 release and the cell‐to‐cell spread of virus from epithelial cells to lymphocytes is mediated by interaction of lymphocyte receptor function‐associated antigen‐1 with the epithelial cell receptor intercellular adhesion molecule‐1. Thus, mucosal epithelial cells may serve as a transient reservoir for HIV, which could play a critical role in viral transmission.     

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。     

Oral mucosal Langerhans'' cells as target, effector and vector in HIV infection

The mechanism underlying a transition of the oral cavity mucosal epithelium towards susceptibility to opportunistic infections in HIV-seropositive patients was investigated. Phenotypic markers CD1a, HLA-DR, and CD86 of oral mucosal Langerhans' cells (LCs), p17 core protein of human immunodeficiency virus (HIV), and CD45RO of memory T cells were labeled on oral hairy leukoplakia lesional biopsies and clinically normal autologous tissue of HIV-infected patients. HIV p17 protein was detected in association with mucosal LCs, mainly within the lesional epithelium. There were significant correlations between the detection of HIV p17 and the depletion of LCs, and between the depletion of LCs and the presence of hairy leukoplakia lesions. Conjugates of activated LCs and memory T cells were also evident in the submucosal area of lesional biopsies. The findings from this study support the hypothesis that oral mucosal LCs are also the target of HIV infection. Cytopathic changes of LCs caused by productive HIV infection may contribute to selective depletion of LCs, which may impair the mucosal immunologic protection against colonization by microorganisms causing HIV-associated oral mucosal lesions.     

Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren’s syndrome but decreased by HIV infection

Calprotectin levels were determined in whole saliva from patients predisposed to oral candidiasis due to HIV infection or Sjögren’s syndrome and from patients with candidiasis associated with various oral disorders (e.g. lichen planus, oral ulceration). Mean calprotectin levels were higher in whole saliva (2 μg/ml) than in parotid saliva (0.3 μg/ml). Oral candidiasis was associated with raised whole saliva calprotectin levels in all groups studied. HIV infection was associated with lower levels of salivary calprotectin, in the presence of high or low salivary Candida counts, although CD4⁺ lymphocyte counts did not significantly correlate with calprotectin concentrations. Calprotectin levels were elevated in saliva from Sjögren’s syndrome patients with oral candidiasis, consistent with mucosal transudation of calprotectin from inflamed mucosa and limited dilution due to decreased salivary flow rates. This study indicates that oral candidiasis is associated with raised calprotectin levels secondary to mucosal inflammation, but that diminution of this candidacidal factor due to HIV infection may be a predisposing factor in the aetiology of oral candidiasis.     

Oral lesions as indicators of HIV infection among routine dental patients in Lagos, Nigeria

OBJECTIVES: To document the incidental oral lesions of human immunodeficiency virus (HIV) infection, the pattern and frequency of the lesions based on clinical presentation and oral manifestations in routine dental patients who tested positive in Nigeria. SUBJECTS AND METHODS: The study was conducted at the Oral Diagnosis/Oral Medicine clinic of the Lagos University Teaching Hospital, Lagos, Nigeria between May 2002 and April 2003. During this period, all patients with oral lesions suggestive of HIV/acquired immunodeficiency syndrome (AIDS) as described in the EEC-WHO Classification and diagnostic criteria of oral lesions of HIV were counseled and offered voluntary HIV testing. All the 35 patients who consented and tested positive were included in this study. RESULTS: Of a total of 700 patients 53 patients with oral lesions suggestive of HIV/AIDS were seen, thirty-eight (72%) consented to HIV screening, 15 patients (28%) refused. Thirty-five patients (92%), mean age 36 +/- 13 years were confirmed positive for HIV. Oral candidiasis was the commonest lesion seen (43%) the second common being Herpes zoster (23%). Other lesions seen included erythema multiforme in two (6%), facial palsy in two (6%) and oral hairy leukoplakia in one (3%). CONCLUSION: An oral mucosal lesion may be the presenting lesion of HIV/AIDS in routine patients attending the dental clinic. Oral health care workers should practice optimal infection control based on the Centers for Disease Control 'Standard Precautions' guidelines on infection control for all patients to minimize occupational transmission of HIV.     

Common oral opportunistic infections in Human Immunodeficiency Virus infection/Acquired Immunodeficiency Syndrome: Changing epidemiology; diagnostic criteria and methods; management protocols

There were 36.9 million in the world living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) as of 2017, and new infections have seen a reduction by 18% since 2010. But this rate of decline is not sufficient for the goal of eradication of AIDS by 2030. Only 21.7  million people infected with HIV have accesses to antiretroviral therapy, with the rest at risk of the potential complications of HIV infection. It has been shown that oral lesions are diagnostic and prognostic of HIV infection, and many oral opportunistic infections continue to be a major problem, particularly in developing countries. It is therefore important that dental surgeons be aware and updated to recognize and manage the oral effects of HIV infection/AIDS. This chapter describes the classification, diagnosis, and management of oral lesions in these patients, based on our current understanding of the infection. This review also discusses the standardization of diagnosis of oral lesions in HIV infection/AIDS patients, immune reconstitution inflammatory syndrome case definition, and the research priorities formulated at the 7th World Workshop on Oral Health and Disease in AIDS.     

Oral innate immunity in HIV infection in HAART era

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human β‐defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co‐infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV‐associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co‐infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART?     

Epstein–Barr virus and human immunodeficiency virus-negative oral plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is an unusual subtype of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphoma that was first described in the oral cavity. HIV-related lymphomas are frequently associated with Epstein-Barr virus (EBV). Recently, dual infection with EBV and human herpesvirus 8 (HHV8) has been demonstrated in PBL. So far, a few cases of PBL occurring in an HIV-negative patient have been documented and all of them were associated with immunosuppression status and/or EBV infection. Here we report a EBV and HHV8-negative oral PBL occurring in an immunocompetent HIV-negative male, which would be the first case.     

Oral candidal infection as a sign of HIV infection in homosexual men

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.     

Oral infectious diseases: a potential risk factor for HIV virus recrudescence?

As the highly active antiretroviral therapy (HAART) has transitioned human immunodeficiency virus (HIV) infection into a 'chronic disease' management strategy, there is growing evidence that infection with non-HIV pathogens in HIV+ patients may have important public health implications in undermining HAART success and acquired immunodeficiency syndrome progression. Several bacterial and host cell products during infections with non-HIV pathogens have shown the capacity to regulate HIV replication in latently infected cells. A high prevalence of oral infections caused by bacteria, viruses and fungi has been described in HIV+ patients, including periodontal disease. The oral cavity appears to be a site of HIV pathogenesis and potential reservoir for the disease as HIV RNA and DNA forms are present in saliva as well as in gingival crevicular fluid, and oral epithelial cells are susceptible to either cell free or cell-associated HIV infection. The clinical and biological bases of potential associations between chronic oral inflammatory disorders, such as periodontal disease, and exacerbation of HIV viraemia have received little attention. This review attempts to evaluate the current understanding of HIV reactivation as a result of co-infection and/or inflammation induced by non-HIV pathogens in HIV-infected patients, and presents a hypothetic model about the potential role of periodontitis as a global oral infection that potentially contributes to HIV recrudescence.     

Head and neck malignancies associated with HIV infection.

Immunosuppressed persons are at greater risk of developing malignancies. In human immunodeficiency virus (HIV) immunosuppression the most common oral cancers are Kaposi's sarcoma and non-Hodgkin's lymphoma. Squamous cell carcinoma has also been reported to be associated with HIV disease. Kaposi's sarcoma is the most frequent neoplastic disease in acquired immunodeficiency syndrome and is by far the most common in the head and neck area. This article reviews the prevalence, clinical features, and management of these diseases in HIV infection.     

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.     

Oral manifestations of HIV infection in 600 South African patients

Arendorf TM, Bredekamp B, Cloete CAC, Sauer G: Oral manifestations of HIV infection in 600 South African patients. J Oral Pathol Med 1998; 27: 176-9. C Munksgaard, 1998. Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse on Oral Problems related to HIV infection and the WHO Collaborating Centre on Oral manifestations of the immunodeficiency virus, were studied in 600 consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%, hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those reported elsewhere, but socio-cultural differences allowed no reliable comparison. More than a quarter of our patients had oral soft tissue discomfort necessitating treatment; in 3.3% these were the presenting symptom. This indicates a potential major public health concern requiring education in recognition and appropriate referral and management.