Oral ulceration in HIV infection: Investigation and pathogenesis

Oral ulcerations associated with HIV infection include recurrent aphthous ulcers (RAU). Whereas RAU prevalence is not increased, lesion severity is: among a group of HIV⁺ patients, 66% had the more severe herpetiform or major RAU. This increased severity suggests that HIV disease-related changes in the immune system may exacerbate RAU. In the peripheral blood of healthy subjects with RAU, CD4:CD8 cell ratios may be reversed and the proportion of T cell receptor-γδ⁺ cells increased. HIV disease-related immune system changes are characterized by reversed CD4:CD8, lowered CD4 cell counts and an inverse correlation between CD4 cell counts and per cent activated γδ lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNFα production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNFα levels are increased. Thalidomide, which inhibits TNFα production, is effective treatment for RAU. Some RAU patients have vitamin B12 or folate deficiencies, levels of which are commonly low in HIV⁺/AIDS patients. However, in a case control study of HIV⁺ patients, vitamin B12- or folate-deficiencies were not found to be significant risk factors for RAU.     

HIV感染者和AIDS患者口腔非特异性溃疡

目的:口腔非特异性(NOS)溃疡是一类与H IV感染有关的口腔病变,其临床表现不同于常见口腔溃疡。通过对NOS口腔溃疡临床特征的分析,为临床医师提供鉴别诊断。方法:回顾性分析72例H IV/AIDS患者,NOS口腔溃疡有3例,探讨其临床特征并与复发性阿弗他溃疡、单纯疱疹性口炎进行比较,探讨其发病机制。结果:NOS口腔溃疡的好发部位为软腭、口咽及舌腭弓处,常为1~2个,病程较长,CD4 细胞明显减少,多伴发白色念珠菌感染。结论:NOS口腔溃疡的发病部位、病程与预后较为特殊,与AIDS的病程进展有一定的联系。     

Oral aspects of HIV infection in children

Most infants with congenital HIV infection appear normal at birth. Clinical difficulties usually begin as the first year proceeds, and in about half of the children oral manifestations are the first signs. Oral manifestations are commonly found in HIV-positive asymptomatic and pediatric AIDS patients, they are the earliest clinical signs of HIV infection and disease progression in children, and may be used as diagnostic markers, especially in developing countries. Studies have established an accurate association between oral manifestations and progression of HIV disease in children. Since the mouth is easily accessed for clinical examination, the important oral signs should be utilized in the diagnosis and early intervention of AIDS in these vulnerable populations.     

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.     

Oral enterobacteriaceae in patients with HIV infection

160 oral swabs of 149 HIV-infected patients and 168 swabs of 166 controls were cultured to detect a possible colonization of the oral cavity with yeasts and Enterobacteriaceae. In 5.0% of the HIV-infected patients and in 4.8% of the controls different species of Enterobacteriaceae were found. Yeasts were always associated with Enterobacteriaceae in the group of HIV-infected patients. Clinically, different oral lesions were seen in the study group. A correlation between the nature of these lesions and the presence of Enterobacteriaceae could not be found. A possible pathogenic role of the Enterobacteriaceae associated with these oral lesions is yet uncertain and remains to be established by further studies.     

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 ulcers in HIV-positive Peruvian patients: an immunohistochemical and in situ hybridization study

Background:  This study describes the histopathological, immunohistochemical (IHC) and in situ hybridization (ISH) data of 25 cases of oral ulcers in HIV-positive patients, with clinical and microscopical features similar to ulcers not otherwise specified (NOS)/necrotizing ulcerative stomatitis (NUS).
Methods:  Sex, age and clinical history were obtained from the clinical records. Histological analysis for H&E, Gomori–Grocott and Ziehl–Neelsen stains, IHC analysis to detect infectious agents and to characterize inflammatory cellular infiltrate, and ISH for cytomegalovirus (CMV) and EBER1/2 were performed.
Results:  Twenty-one patients were men and four were women (mean age of 34.6 years). The tongue was preferentially affected. Microscopically, the lesions showed extensive necrosis, leukocytoclasia, vasculitis with luminal fibrin clots and an intense inflammatory cellular infiltrate predominated by CD68⁺ atypical large cells, normal-sized and crescent-shaped nuclei macrophages, interspersed by CD8⁺ T lymphocytes. Mast cells were also observed in all samples studied. CD4⁺ T lymphocytes, CD20⁺ B lymphocytes and VS38c⁺ plasma cells were practically absent. CMV and EBER1/2 were identified in scarce cells of 3 and 16 of 25 cases respectively.
Conclusion:  These results show that CD68⁺ macrophages, followed by CD8⁺ T lymphocytes, were the predominant inflammatory cells, indicating they are relevant to the pathogenesis of the ulcers, possibly reflecting an abnormal immune response in the oral mucosa. The clinicopathological and immunoprofile features of the present cases are similar to NOS ulcers/NUS in HIV-positive patients.     

Oral manifestations of HIV infection in 75 Dutch patients

Seventy-five consecutive HIV-infected patients, including 33 AIDS cases were examined. One or more oral mucosal lesions were observed in 57 (76%); candidiasis was the most common finding (52%). Others included hairy leukoplakia (16%), periodontal disease (16%) and Kaposi's sarcoma (4%). Diversity of study design and methods allowed no reliable comparison with other reports.     

Facial and perioral molluscum contagiosum as a manifestation of HIV infection

Molluscum contagiosum (MC) is a self-limiting viral disease of the skin and the mucous membranes. Facial and perioral MC is seen with increasing frequency in human immunodeficiency (HIV) infection, particularly in HIV infected homosexual men. The purpose of this study was to describe clinical observations of facial and perioral MC in HIV infected patients. One hundred and eighty HIV-positive individuals (160 males and 20 females) were examined over a period of five years. Fifty-eight were homosexual men and 19 were bisexual men. Fifty-one of 180 patients at the time of the first examination had CD+4 count < 200 cells/mm3 and another 63 presented loss of CD+4 cells in this level, during this period. Three HIV infected patients (two homosexual and one bisexual) were affected with facial and perioral MC. At the time of MC diagnosis the CD+4 count was less than 200 cells/mm3 for all three patients. One patient died nine months after MC diagnosis and the other two are still alive. It is remarkable that in this study no clinical lesions were observed on other sites of the skin.     

Oral manifestations in 101 Cambodians with HIV and AIDS.

BACKGROUND: The HIV/AIDS epidemic in Cambodia has become a major problem in the last 7-8 years, mainly because in this formerly war-stricken country the socioeconomic situation is only slowly improving. Since only very few studies have been published to date on the oral health status of Cambodian HIV/AIDS patients, it was the purpose of the present investigation to study oral manifestations in Cambodian patients with HIV disease. METHODS: One hundred one Cambodian patients with HIV infection or AIDS were examined for the presence of oral manifestations in one medical center in Phomh Penh, Cambodia. RESULTS: Sixty-three men and 38 women with a median age of 32 years were examined (age range 7.5-63.5 years). Of these patients, 42.6% were smokers, 46.5% of men were heavy drinkers and 90.5% of men were promiscuous compared with 5.3% of women. The most frequent AIDS-defining diseases were wasting syndrome (54.5%), Pneumocystis carinii pneumonia (PcP) (19.8%) and tuberculosis (18.8%). Puritic papular eruption, a common cutaneous manifestation in HIV-infected patients, was seen in 17.8% of patients. Candida-associated infections of the oral cavity were most common. Among the patients, 52.5% revealed pseudomembranous candidiasis and 35.6% had bilateral hairy leukoplakia. Only 10% of patients had no oral lesions. Also common were necrotising ulcerative gingivo-periodontal diseases (27.7%). CONCLUSION: The general health status of 101 Cambodian patients with HIV infection and AIDS was poor, and they demonstrated a large number of oral manifestations. Antiretroviral therapy is presently not available and only a fraction of patients receives antimycotic treatment (25.7%). HIV infection and the AIDS epidemic in Cambodia have become a serious problem and patients urgently need adequate diagnosis and antiretroviral therapies.     

Non-surgical management of an oro-antral fistula in a patient with HIV infection

BACKGROUND: The risk of post-extraction complications is higher in patients who are immunosuppressed compared to other patients with normal immune function. In addition, invasive dental procedures are more likely to have serious complications in these patients. This case report demonstrates an effective non-surgical procedure to treat an oro-antral fistula in an HIV-infected man. METHODS: The oro-antral fistula was de-epithelialized under local anaesthesia and the patient wore a surgical splint continuously, removing it only for cleaning, for an eight week period. Chlorhexidine gel was regularly applied to the fitting surface of the splint and the oro-antral communication. The patient was reviewed on a regular basis. RESULTS: This procedure resulted in resolution of the patient's symptoms within two weeks. Complete healing of the oro-antral fistula was evident following eight weeks of wearing the surgical splint. CONCLUSIONS: This procedure provided an effective method of treating an oro-antral fistula in an immunocompromised patient without causing any detrimental effects to the patient's overall health. Adequate pre-surgical assessment of patients prior to extractions is important in all patients to help prevent the occurrence of such complications.     

Pseudomembranous oral candidiasis in HIV infection: Ultrastructural findings

A light and electron microscopic investigation of pseudomembranous candidiasis in HIV infection was undertaken as there is little data available on the ultrastructural features of the invasive phase of Candida in this disease. On examination of biopsy specimens of four patients, histopathology revealed the classic features of superficial candidiasis, including hyphal penetration down to the spinous cell layer, parakeratosis, acanthosis and spongiosis of the infected, superficial epithelium. However, in one case, hyphae traversed the entire epithelium and crossed the basal membrane, invading the adjacent connective tissue. Ultrastructural investigations revealed initial hyphal penetration through the intercellular spaces, possibly demonstrating thigmotropism. However, hyphal penetration was not solely confined to intercellular spaces, as some specimens demonstrated hyphal elements traversing both the cytoplasm and the nuclei of the spinous cells. In these areas of the epithelium appressoria-like appendages were often found at the hyphal tip. These phenomena, commonly described in plant fungi, have rarely been described in human material. Pools of desmosomes were seen in the vicinity of the hyphal pathways, implying that the penetration procedure is associated with detachment and congregation of desmosomes, possibly by enzymatic means. Interestingly, the host immune response to fungal invasion appeared to be minimal, as no immune-effector cells were seen closely associated with either the blastospores or the hyphae in any of the tissues examined. Whether the foregoing events are exaggerated by the abortive immune response seen in HIV-infected patients, or common in immunocompetent individuals during candidal invasion of epithelia, needs to be ascertained by further studies.     

Herpes zoster in HIV infection with osteonecrosis of the jaw and tooth exfoliation

BACKGROUND: Herpes zoster (HZ) infection of the trigeminal nerve is associated with complications such as postherpetic neuralgia, facial scarring, loss of hearing ability and conjunctivitis. Until 2005, postherpetic alveolar necrosis and spontaneous tooth exfoliation have been described in 20 cases unrelated to HIV infection. OBJECTIVE: The aim of this study was to describe HIV infection in patients (two women, two men, average age 30 years) who suffered from HZ attacks to their trigeminal nerves. MAIN OUTCOME MEASURES: None of the patients had received antiherpetic medications or antiretroviral therapy. HIV infection was only diagnosed after the development of HZ. Facial scarring with depigmentation and hyperesthesia (postherpetic neuralgia) was diagnosed in all four patients. Oral findings consisted of spontaneous loss of both maxillary or mandibular teeth. Osteonecrosis of varying extent was also found. Treatment consisted of extractions of teeth and administration of antibiotics and analgesics. Healing of alveolar wounds was unremarkable. CONCLUSION: Complications affecting the alveolar bone and teeth seem to be rare in HIV-infected patients.     

Cytomegalovirus associated oral ulcerations in HIV-infected patients

Oral ulcerations associated with disseminated cytomegalovirus (CMV) infection were observed in four patients with AIDS manifestations showing low CD4 counts. Virus cultures of urine and saliva samples were positive for CMV in all cases. The lesions were characterized by a punched-out appearance, non-indurated borders, low bleeding tendency and lack of inflammatory wall. Light microscopy revealed granulation tissue containing "owl's eye" like cells in all specimens. Presence of CMV was confirmed by immunohistochemistry and in situ hybridization. The ulcerations were infiltrated with T-lymphocytes of the helper, suppressor and cytotoxic subset, most were positive for HLA DR. Despite the local invasion with immunocytes and high serum titers of serum antibodies the patients experienced progressive CMV disease.     

Oral manifestations of HIV infection in a group of predominantly ethnic Chinese

A total of 32 HIV-infected, predominantly ethnic Chinese individuals from Hong Kong were examined for oral mucosal lesions over a period of 1 year. The commonest oral lesion found was minor aphthous ulceration (27.4%), while xerostomia (17.8%), ulceration NOS (not otherwise specified; 12.3%), hairy leukoplakia (11.0%) and erythematous candidiasis (6.9%) were less frequent; Kaposi's sarcoma was notable for its absence. When the relationship between the number of oral lesions with age, risk group, medication taken, CDC staging and CD4+ count of the study group was investigated, a significantly higher number of oral lesions was associated with use of AZT, homosexuals and CDC stage IV; in contrast, a smaller number of lesions was found in those on antiparasitics and multivitamins (all P<0.05). When compared with studies from other parts of the world, the frequency of oral lesions appeared to be less common in the current study group. However, due to a lack of similar studies from the Asian region, especially in ethnic Chinese, it is not clear whether this difference could be attributed to racial, social or geographic factors.     

Oral candidiasis and human immunodeficiency virus infection

The association of oral candidiasis with the human immunodeficiency virus (HIV) infection has been known since the advent of the acquired immunodeficiency syndrome (AIDS) pandemic. Oral candidiasis is one of the earliest premonitory signs of HIV infection and its diagnosis may have grave prognostic implications for the eventual development of full blown AIDS. There is now an expanding body of data on novel clinical variants of this 'old' disease, its epidemiology in HIV seropositive individuals and, advances in its management, particularly with respect to the recently introduced bis-triazole antifungals. Current concepts pertaining to the epidemiology, clinical features, pathogenesis, laboratory diagnosis and management of oral candidiasis in HIV infection are reviewed.     

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.     

72例HIV/AIDS口腔病损的临床观察

目的：分析HIV感染者和AIDS患者常见口腔病损,以期提高临床医师对AIDS早期临床表现的认识,提高早期诊断准确性。方法：回顾分析72例HIV／AIDS患者临床症状、体征和实验室检查,分析口腔病损在AIDS早期诊断中的意义及与病程进展的关系。结果：常见口腔病变有：口腔白色念珠菌病、疱疹性口炎、非特异性口腔溃疡,其它病损如颌面部淋巴结炎、毛状白斑、卡波济肉瘤、带状疱疹、涎腺肿大,牙周病等,可单发或同时伴发。全身系统性疾病主要包括：肺炎、慢性腹泻、结核等。结论：AIDS患者发病前已开始出现明显口腔表现,其中以口腔白色念珠菌感染最为常见,对非法采供血、输血、静脉吸毒或不安全性行为等特殊人群,如出现难以治愈的”霉菌性口炎”或反复发作、原因不明的疱疹性口炎,或出现毛状白斑、卡波济肉瘤等口腔病变,应及时进行HIV检测。