The significance and management of periodontal lesions in HIV infection

It is now almost 20 years since we reported the existence of a previously unknown lesion, oral hairy leukoplakia, and its unexpected nature as the only human disease in which there is prolific replication of the gamma-herpesvirus, Epstein–Barr virus (EBV). Since then, it has become clear that, in the HIV-infected population, oral lesions are of particular significance. Their presence in individuals of unknown HIV serostatus is highly suggestive of HIV infection, while in people who are known to be HIV-infected, the development of oral candidiasis or hairy leukoplakia – often the very first lesions to occur – indicates that the battle between HIV virion production and destruction of immunologically important cells on, versus replacement of those cells has shifted in favour of HIV. These observations have led to the almost universal inclusion of oral lesions in staging and classification schemes for HIV infection. Recently, lower frequencies of oral disease have been seen in those on HIV therapy, except that oral warts may become more common as the viral load falls and CD4 count rises.
OBJECTIVES: To review the significance and management of periodontal lesions seen in HIV infection.
DESIGN: Traditional review.
RESULTS: HIV-associated periodontal lesions may be categorised as unusual forms of gingivitis, necrotizing periodontal diseases and exacerbated periodontitis. These lesions are significant in the extent to which they mark the underlying HIV disease and have service planning implications. Only limited data are available to inform guidelines for the management of individual patients.
CONCLUSIONS: Research of the effectiveness of interventions for HIV-associated periodontal lesions is needed.     

Oral manifestations in HIV-positive adults from Northern Thailand

Eighty-seven HIV-infected patients in a provincial hospital in Northern Thailand were examined for oral manifestations of HIV disease and AIDS. The median age was 31.3 years. Seventy-four of the patients were women, 13 were men. 96.6% had a history of heterosexual transmission. Sixty-one patients were CDC-category A, 20 were category B and 6 were category C (AIDS). Thirty-eight percent of the patients revealed oral lesions; 23% had one oral lesion and 13.8% had two oral lesions. Common lesions were oral candidiasis (10.3% pseudomembranous candidiasis, 6.9% erythematous candidiasis and 3.4% both forms), oral hairy leukoplakia (11.5%) and exfoliative cheilitis (6.9%). Gingival linear erythema was seen in 8% of the patients; periodontal lesions and necrotising ulcerative gingivitis were not observed. Men were more commonly affected by oral manifestations than women (P < 0.004). The spectrum of oral lesions is comparable to other studies from the region, although most of these reported more men than women. Also, the degree of immunosuppression was more marked (AIDS).     

Classification and diagnostic criteria for oral lesions in HIV infection

A consensus has been reached on the classification of the oral manifestations of HIV infection and their diagnostic criteria, based on presumptive and definitive criteria. The former relate to the initial clinical appearance of the lesion and the latter are often the result of special investigations. Candidiasis, hairy leukoplakia, specific forms of periodontal disease [linear gingival erythema, necrotising-(ulcerative) gingivitis and necrotising(ulcerative) periodontitis], Kaposi's sarcoma and non-Hodgkin's lymphoma are strongly associated with HIV infection. Lesions less commonly associated with HIV infection and lesions seen in HIV infection, but not indicative of the disease, are also listed.     

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.     

Prevalence and incidence of oral lesions--the changing scene

A range of oral mucosal and periodontal lesions is associated with HIV infection and HIV disease progression. These are often symptomatic and require treatment in themselves, and also have a diagnostic and prognostic role in the management of the underlying HIV disease. These lesions have been broadly divided into: (a) those strongly associated with HIV such as oral candidoses, oral hairy leukoplakia and Kaposi's sarcoma; (b) those less strongly associated such as swellings of the major salivary glands; and (c) those least commonly associated such as recurrent aphthous ulcers. Overall the prevalence and severity of these lesions inversely correlate with the level of immunosuppression. With the passage of time, there has been improved understanding of the disease pathogenesis resulting in the development of new drugs to combat this infection. Medication has changed from monotherapy to current triple combination therapy (Highly Active Anti-Retroviral Therapy). This review looks at the impact of changing therapy on the prevalence of the various oral lesions associated with HIV. It finds a decrease in the prevalence of the oral lesions in the era of combination therapy as compared to earlier periods. It also shows a change in the types of lesions which predominate with those previously placed amongst the strongly associated lesions no longer being predominant in the era of combination therapy where such treatment is available.     

Demonstration of Epstein-Barr virus in scrape material of lateral border of tongue in heart transplant patients by negative staining electron microscopy

Scrape material from the lateral border of the tongue of 50 heart transplant patients and 20 controls was studied for the presence of EBV by negative staining electron microscopy. Mild oral hairy leukoplakia was observed in two cases. Particles of the herpes virus were found in 20% of the specimens. Controls were negative for EBV. The study has shown that EBV may be expressed at the lateral border of the tongue during immunosuppression, occasionally resulting in the clinical appearance of hairy leukoplakia.     

Epstein–Barr virus prevalence in oral squamous cell cancer and in potentially malignant oral disorders in an eastern Hungarian population

We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) against 68 age-matched controls for the presence of Epstein–Barr virus (EBV). Apparently healthy mucosa was simultaneously sampled and examined in all patients. Paraffin-embedded tissue sections of all EBV-positive patients with OSCC were examined for latent membrane protein-1 (LMP-1) expression (demonstrable in most EBV-associated malignancies) using immunohistochemistry. The prevalence of EBV in the controls and in OSCC, OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%, 22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence of EBV in OSCC patients was significantly higher than in controls or in respective samples of the other two patient groups both in the lesion and in the healthy mucosa. Comparisons including only patients with EBV-negative lesions yielded similar results. Lesions of patients with OLP, but not of patients with OL, differed significantly from controls in EBV prevalence. In OSCC, LMP-1 expression was not detected, and EBV carriage was not significantly associated with any risk factors and did not influence the outcome. Although a high prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa of patients indicated that an aetiological role of EBV is unlikely.     

HIV-associated oral lesions; immunologic, virologic and salivary parameters

There are numerous reports of oral lesions in HIV-infected individuals. However, few correlate the oral lesions with laboratory parameters. This study examined oral candidiasis and hairy leukoplakia, the two most common HIV-associated oral lesions, in relation to T-cell counts, p24 core antigen levels and salivary flow rates. Oral mucosal examinations, immunologic and virologic studies and stimulated whole and parotid saliva flow rates were conducted on 135 (HIV+ = 102, HIV- = 33) homosexual or bisexual men. Results indicate that, among HIV-infected subjects, the odds of having oral candidiasis is 6 times (95% CI = 0.6-56.6) greater for subjects with T4 counts between 200-399 per mm3, and 23 times (95% CI = 2.8-193.0) greater for subjects with T4 counts less than 200/mm3 compared to subjects with T4 counts of 400/mm3 or greater. Subjects had an equal likelihood of having hairy leukoplakia at different levels of immunocompetence. The prevalence of oral candidiasis and hairy leukoplakia was higher among subjects with infectious virus in their serum, but was only statistically significant for hairy leukoplakia (p = 0.01).     

Oral manifestations of an HIV positive cohort in the era of highly active anti-retroviral therapy (HAART) in South London

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is associated with oral manifestations of diagnostic and prognostic importance. With the advent of Highly Active Anti-retroviral Therapy (HAART) there is anecdotal evidence to suggest that the prevalence of oral lesions has declined. The number of prevalence studies, carried out in the era of HAART is, however, meagre. Our aim was to study the prevalence of the oral manifestations of HIV in a population, predominantly on HAART, attending a Genito-Urinary Medicine Centre in South London. METHODS: This cross sectional study included 203 adult volunteers, comprising 76% males and 24% females. One third of the subjects were from the predominantly African or Afro- Caribbean ethnic minority groups resident in London. The relationship between the prevalence of oral lesions and demographic variables, therapeutic regimes, viral load and CD4 counts were evaluated. RESULTS: One hundred (49%) of the patients had no detectable oral lesions. Oral lesions detected most frequently included oral hairy leukoplakia (9.9%), HIV associated periodontal diseases (9.9%) and oral candidiasis (4.9%). Three subjects had multiple papillomatous growths. Most cases (n = 17/20) of oral hairy leukoplakia were in individuals with a detectable (> 400 copies/ml) plasma RNA viral load. The majority (n = 8/10) of our patients with oral candidiasis had a plasma RNA viral load > 10,000 copies/ml and half (n = 5/10) had a CD4 count < 200 cells/mm3. Logistic regression analysis suggested that the presence of an oral lesion was not associated with any demographic features except for periodontal diseases which were associated with tobacco smoking (P = 0.023). CONCLUSIONS: The prevalence of so called 'strongly associated' oral lesions of HIV is low in this South London HIV-infected population on HAART, and the relative frequency is different from that cited in the literature from the pre-HAART era. The oral lesions detected were found mostly in people with low CD4 counts and high HIV-1 RNA viral loads, suggesting they were very immunocompromised, not on, or declining therapy, or that their therapy was failing.     

Sentinels and signposts: The epidemiology and significance of the oral manifestations of HIV disease

A large number of studies attest to the frequency of oral disease in those with HIV infection. Most show that hairy leukoplakia and pseudomembranous candidiasis are the commonest lesions in those with HIV infection and AIDS, with higher prevalence and incidence rates correlating with falling CD4 counts and disease progression. HIV-infected individuals with oral candidiasis or hairy leukoplakia progress to AIDS more rapidly than matched controls without these lesions. Oral candidiasis and hairy leukoplakia increase with time since seroconversion. On the other hand, parotid enlargement in children appears to be associated with slower progression to AIDS. As a consequence of these and other observations, oral lesions are widely included in natural history studies, staging and classification schemes for HIV infection. In addition to their role in the diagnosis of HIV infection and as indicators of the progression of HIV disease, oral lesions are used as clinical correlates of CD4 counts and as criteria for entry into clinical trials.     

Oral manifestations in 70 German HIV-infected women

OBJECTIVE: To describe the prevalence of oral lesions in HIV-infected women, and to determine the association of oral lesions with the level of immunosuppression and the route of transmission. PATIENTS: In a retrospective, cross-sectional study, a cohort of 70 HIV-infected women (median age: 32.5 y; median CD4⁺-cell count 262 per μl) comprising 18% of all HIV-infected individuals (n = 389) was selected in an outpatient clinic. Oral lesions strongly associated with HIV-infection were evaluated. RESULTS: The overall prevalence of oral lesions was 27/70 (39%). Among HIV-infected women with CD4⁺-cell counts <200 per μl, the prevalence was 65% (19/29); and with counts >200 per μl, the prevalence was 27% (11/41). The prevalence of candidiasis and hairy leukoplakia was similar among those infected heterosexually or by intravenous drug use. CONCLUSIONS: As reported in men, these findings demonstrate that oral lesions are common in HIV-infected women. Candidiasis is more likely to occur at low CD4⁺-cell counts, whereas no difference was seen regarding the level of immunosuppression and hairy leukoplakia. Interestingly, the route of transmission does not play a role regarding the presence of oral lesions among HIV-infected women.     

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 lesions and conditions associated with human immunodeficiency virus infection in 300 south Indian patients

BACKGROUND: Human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) is a major health problem in India. The National AIDS Control Organisation (NACO) of India reports a seropositivity of 25.03 per thousand for the whole country, as of October 1999. In spite of this high prevalence there are very few reports of oral lesions and conditions in Indian HIV/AIDS patients, which are important in early diagnosis and management of these patients. OBJECTIVE AND SETTING: The present report describes the oral lesions in 300 HIV positive symptomatic patients presenting to us at RAGAS-YRG CARE, a non-governmental organisation in Chennai, South India, over a period of 9 months in 1998. METHOD: Lesions were diagnosed on clinical appearance using international criteria. RESULTS: Of the 300 patients 89% had acquired the infection through heterosexual contact. There were 205 males and 95 females, aged from 7 months to 72 years. Forty-seven percent of the patients were in the age group 21-30 years. CD4 counts were ascertained for 105 patients, 64 (62%) had CD4 counts < or = 200. A total of 217 (72%) of the 300 patients had some oral lesion when examined. Gingivitis (47%) and pseudomembranous candidiasis (33%) were the most common oral lesions. The other oral lesions seen were oral mucosal pigmentation (23%), erythematous candidiasis (14%), periodontitis (9%), angular cheilitis (8%), oral ulcers (3%), oral hairy leukoplakia (3%), hyperplastic candidiasis (1%), oral submucous fibrosis (2%) and one case of leukoplakia. CONCLUSIONS: Oral lesions occur commonly in HIV infection. A comprehensive oral examination may not only suggest HIV disease but may also be useful in monitoring the disease progression. This is a cost-effective procedure, which may be useful in screening large populations in developing countries like India.     

Oral lesions in Mexican HIV-infected patients

One hundred and twenty-five HIV-infected patients, of whom 49 (39%) were at early stages of the infection (CDC-II & III) and 76 (61%) in CDC IV, were prospectively examined. In 100 (80%) one or more oral mucosal lesions were observed; candidiasis (51%) and hairy leukoplakia (43%) were the commonest. Erythematous candidiasis was more often seen (35%) than the pseudomembranous type (16%), and appeared with the higher values at early than later stages. The prevalence of hairy leukoplakia, oral hyperpigmentation and xerostomia were incremented in groups CDC-IV. Pseudomembranous candidiasis and exfoliative cheilitis increased significantly with severity of disease. Our study demonstrates that oral alterations associated to HIV are a frequent finding, both at early (76%) and late (83%) stages of the infection in Mexican patients.     

Classifications of oral lesions in HIV infection

BACKGROUND: Manifestations of immunosuppression may take the form of opportunistic infection, and neoplasia. While this paper has focused on gingival and periodontal manifestations. these tissues cannot be evaluated in isolation. The presence of involvement of other oral tissues such as the cheek or tongue with manifestations associated with HIV such as hairy leukoplakia, Kaposi's sarcoma at these sites, and candidiasis in addition to periodontal manifestations may further increase the clincal suspicion of underlying immunosuppression and/or progression of the immunosuppressive state. DISCUSSION: The periodontist plays an essential r le in identifying the periodontal status of an individual and has an important r le to play in early recognition of signs and symptoms of HIV disease or progression of the medical condition. CONCLUSION: Only through such recognition can appropriate definitive diagnostic testing be conducted, and appropriate therapeutic intervention for the oral condition and the systemic condition be considered.     

Oral manifestations in HIV/AIDS infected patients from India

OBJECTIVES: To assess types and prevalence of HIV-related oral lesions among HIV-infected individuals in south India and to correlate common oral findings with co-morbidities, gender, age and medication. SUBJECTS AND METHODS: One hundred and one patients with HIV infection or AIDS at infectious diseases units of Attavar Hospital, Mangalore, and medical wards of Kasturba Medical College, Manipal, were selected. Sociodemographic information was obtained using a structured questionnaire. Oral lesions were diagnosed according to the presumptive criteria of EEC-Clearinghouse Classification. Clinical history was retrieved from patient's medical records. RESULTS: Erythematous candidiasis (44.5%), melanotic hyperpigmentaion (34.6%) and xerostomia (29.7%) were among the most common oral manifestations. A significant association was found between oral candidiasis and advanced immunosuppression (P < 0.05). Oral hairy leukoplakia (OHL) was predominant in individuals <35 years (P < 0.05). Melanotic hyperpigmentation was significantly associated with highly active antiretroviral therapy (P < 0.05). OHL was more frequent in patients with HIV-associated tuberculosis. Linear gingival erythema was more predominant in females. CONCLUSIONS: Oral hairy leukoplakia showed a positive relationship with patients younger than 35 years. Oral candidiasis can act as a marker for immunosuppression. Angular cheilitis was predominant in the symptomatic stage.     

Risk factors associated with oral lesions in HIV-infected heterosexual people and intravenous drug users in Thailand

This study aimed to identify factors associated with the presence of oral lesions in HIV-infected individuals in Thailand, to determine the influence of gender and route of HIV transmission on the prevalence of the lesions, and to investigate whether total lymphocyte cell counts can be used as a serologic marker to predict the occurrence of oral lesions. Two hundred and seventy-eight HIV-infected heterosexual persons and intravenous drug users (IVDUs) were enrolled (230 males, 48 females). Eighty-six HIV-free subjects from the same population were included as controls (61 males, 25 females). Oral candidiasis was the most common oral lesion among HIV-infected individuals (39.6%), followed by hairy leukoplakia (HL) (26.3%), exfoliative cheilitis (18.3%), and linear gingival erythema (LGE) (11.5%). Odds ratios (ORs) for factors associated with the presence of oral lesions were as follows for advanced HIV disease defined by clinical status: symptomatic stage [OR= 18.6; 95% confidence interval (CI) 7.3-47.2], AIDS stage [OR 7.3; 95% CI 3.4-15.7] and laboratory investigation of total number of lymphocyte cell counts of 1,000-2,000 cell/mm3 [OR 2.7; 95% CI 1.4-5.1] and <1,000 cell/mm3 [OR 4.0; 95% CI 2.3-7.0], alcohol consumption [OR 3.4; 95% CI 1.3-9.1], and poor oral health [OR 1.7; 95% CI 1.0-2.9]. Men were significantly more likely to have oral lesions than women. No statistically significant difference in the presence of oral lesions was observed between heterosexuals and IVDUs. This study should help predict the risk of acquiring various types of oral lesions, given that the person is exposed to multiple risk factors compared to another who is not exposed to these factors.     

Oral signs and symptoms in 160 Greek HIV-infected patients

One hundred and sixty HIV-infected Greek patients were prospectively examined and the oral signs and symptoms were recorded. At the time of oral examination, 76 patients were asymptomatic seropositive, 47 were in ARC stage and 37 had AIDS. One or more oral findings were recorded in 90.6% of the patients while a total of 33 different lesions were observed. The more common oral lesions (highly suspicious) were candidiasis (61%), hairy leukoplakia (24%), periodontitis (19%), necrotizing gingivitis (11%) and Kaposi's sarcoma (12%). In addition some unclassified lesions or symptoms (xerostomia 26%, burning mouth syndrome 19%, patchy depapillated tongue 16%, hairy tongue 10%, exfoliative cheilitis 4%), were common while submandibular and cervical lymph node enlargement were found in 49% of the patients. Interestingly in 16 patients (10%) the suspicion of HIV infection was exclusively based on oral lesions. Our findings show that oral signs and symptoms are common and some times early manifestations of HIV infection and it is in association to those reported in previous studies.     

Oral diseases, mycology and periodontal microbiology of HIV-1-infected women

HIV-1 infection is increasing more rapidly among heterosexual women. Relatively limited information is available on HIV-related oral pathoses in these individuals. To gain insight into the type and occurrence of oral lesions in this population, 25 HIV-1 infected women including asymptomatic, symptomatic and AIDS patients were examined clinically and sampled for detection of oral yeast and characterization of their subgingival microbial flora. Sixty percent of the subjects were African-American, with 80% infected via heterosexual contact. Oral candidiasis was the most common nonperiodontal oral lesion, observed in 44% of the patients. Oral yeast was cultured from all women with candidiasis and 76% of the total subjects. Oral hairy leukoplakia was clinically diagnosed in 16% of the subjects. Clinically mild to moderate gingivitis and periodontitis were observed in 84% and 52% of the patients, respectively. Candidiasis and the presence of cultivable yeast were observed in patients with low, intermediate, and high CD4⁺ T lymphocyte numbers. Plaque samples were collected from each subject and enumerated by predominant cultivable methods, selective media and microscopy. No differences were detected in the microflora associated with seropositive women with existing periodontitis relative to those without periodontitis or to seronegative women with periodontitis. Candidiasis was the most notable oral clinical manifestation in the HIV-1-infected women and may be a useful clinical indicator of early immune dysfunction mediated by HIV-1.     

Real-time polymerase chain reaction quantification of human cytomegalovirus and Epstein-Barr virus in periodontal pockets and the adjacent gingiva of periodontitis lesions

BACKGROUND: Genomic sequences of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), two herpesviruses, can frequently be detected in periodontal pockets of progressive periodontitis lesions, but the prevalence and load of the two viruses in gingival tissue are unknown. This study determined levels of HCMV and EBV DNA in the periodontal pocket and in the adjacent gingiva of periodontitis lesions using a real-time polymerase chain reaction (PCR) assay. MATERIAL AND METHODS: A total of 20 systemically healthy periodontitis patients participated in the study. Nine patients below 35 years of age were tentatively diagnosed as having aggressive (early onset) periodontitis, and 11 patients 36-56 years of age as having chronic (adult) periodontitis. Clinical parameters were evaluated using established methods. Using periodontal curettes, specimens were harvested from 6-10 mm periodontal pockets and from the adjacent inflamed periodontal pocket wall. A 5'-nuclease (TaqMan) real-time PCR assay was used to identify and quantify genomic copies of periodontal HCMV and EBV. RESULTS: HCMV DNA was detected in 78% of subgingival and 33% of gingival tissue samples from aggressive periodontitis lesions, but only in 46% of subgingival and 9% of gingival tissue samples from chronic periodontitis lesions. In aggressive periodontitis, HCMV subgingival and gingival tissue counts were positively correlated with periodontal pocket depth and probing attachment loss at sample sites (p6 mm, but none of 14 patients having mean pocket depth at sample teeth相似文献