The global changing pattern of the oral manifestations of HIV.

The significance of the oral manifestations of HIV has been widely recognised since the start of the epidemic. It is estimated that more than 38 million people are living with HIV currently, with more than a third presenting with oral manifestations. Access to optimum clinical management and effective treatment in resource-rich countries has led to a remarkable decrease in some of the oral manifestations in the HIV population but this is not mirrored in developing countries, where most HIV-positive patients reside. In this paper, a review of the literature since the start of the HIV infection in different parts of the world is presented to highlight the current significance of the oral conditions in this population. Oral candidiasis was repeatedly reported as the most encountered oral manifestation of HIV in different countries, including in studies on groups on anti-retroviral therapy. Over time salivary gland disease was reported less in developed countries but was encountered more in developing countries. There is evidence to show that the prevalence of oral warts increased with the establishment of anti-retroviral therapy. A review of the worldwide prevalence of HIV-related oral conditions indicates that except for oral hairy leucoplakia, the prevalence of all other nine commonly reported oral conditions remained the same or increased over time. Oral opportunistic infections in HIV-infected patients are an ongoing clinical burden mainly in developing countries. Maintaining research in the subject and improving access to HIV treatment will help address the oral health inequalities around the world.

Oral manifestations of HIV: Can they be an indicator of disease severity? (A systematic review).

OBJECTIVE: To review the existing research literature on the paradigm that the oral lesions could be an indicator of the disease severity with the objective of documenting the current status of research, highlighting its major findings. MATERIAL AND METHODS: Publications were identified through a careful search, of which a majority focused on oral lesions as an indicator for HIV progression. A PubMed journal search of 10 years OF period publication (2009-2019) for "oral lesion, oral manifestation, indicator, HIV and HIV-associated" was performed and analysed. Various research methods were included within the study criteria including clinical study, clinical trial, comparative study and randomised control trial. RESULTS: A total 33 studies were obtained and analysed, including cohort study, cross-sectional study, case-control study, clinical trial, retrospective observational analysis study, prospective observational study and randomised control trial. The most common oral lesions found in the studies were Kaposi sarcoma (KS), followed by oral candidiasis, periodontitis, necrotising ulcerative gingivitis (NUG), necrotising ulcerative periodontitis (NUP) and oral hairy leucoplakia (OHL). The early diagnosis and accurate treatment plan were very important to indicate the disease severity related to HIV infection. CONCLUSION: Oral lesions reported in 39% articles and could be an indicator of HIV disease severity due to its effects on decreased cluster-differentiated (CD4+) T-cell count and increased viral load.

Oral Lesions in Kidney Transplant Recipients

Permanent immunosuppression is necessary to prevent rejection after kidney transplantation. However, it may predispose patients to different conditions and diseases including oral lesions. The most common benign oral lesions in kidney transplant recipients are gingival hyperplasia, oral candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma, although rarely, can also be seen in kidney transplant patients. In this review, we present the incidence, etiology, clinical findings, diagnosis and treatment options for these lesions. For kidney transplant recipients,it is important to maintain good oral hygiene and care, as well as regular professional control by the dentist. This approach can reduce the number and severity of oral lesions.

Smoking as a risk factor for oral candidiasis in HIV-infected adults.

OBJECTIVE: We aimed to examine if smoking is an independent predictor of oral candidiasis (OC) among HIV-1 infected persons. METHODS: The cross-sectional part of this study evaluated 631 adult dentate HIV-1 seropositive persons examined for OC from 1995-2000 at the University of North Carolina Hospitals in Chapel Hill, NC. In the second part, from the above sample, a total of 283 individuals who were free of HIV-associated oral diseases at baseline were followed up for 2 years to assess incident OC events. Data collected from medical record review, interview questionnaires, and clinical examinations were analyzed using chi-squared tests and t-tests. Logistic regression models were developed for prevalent OC employing the likelihood ratio test, whereas Poisson regression models were developed for assessing cumulative incidence of OC. These models included a variety of independent variables to adjust for confounding. RESULTS: Thirteen percent of participants had OC only; 4.6% had OC with Oral Hairy Leukoplakia; and 69.7% had neither. Smoking was associated with OC in all models [prevalent OC - current smokers: logistic regression - Odd ratio (95% CI) = 2.5 (1.3, 4.8); Incident OC - current smokers: Poisson regression (main effects model) - Incidence rate ratio (95% CI) = 1.9 (1.1, 3.8)]. Other Poisson regression models suggested evidence for effect modification between CD4 cell count and incident OC by smoking. CONCLUSION: Smoking is an independent risk factor for the development of OC in HIV-1 infected persons, and the risk of OC is modified by CD4 cell count which measures strength of the immune system.

Orofacial diseases in solid organ and hematopoietic stem cell transplant recipients.

OBJECTIVE: Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at risk of several diseases, principally attributable to immunosuppression. This global overview of SOT/HSCT-associated orofacial diseases is aimed at providing a practical instrument for the oral healthcare management of SOT/HSCT recipients. METHODS: Literature search was made through MEDLINE. The associations between orofacial diseases and SOT/HSCT were assessed using observational studies and case series and were classified into 'association', 'no association', and 'unclear association'. RESULTS: Lip/oral cancers, drug-induced gingival overgrowth (DIGO), infections, including hairy leukoplakia and, less frequently, post-transplantation lymphoproliferative disorders (PTLDs) and oral lichenoid lesions of graft-versus-host disease (GVHD), were associated with SOT. Lip/oral cancers, GVHD, mucositis, DIGO, infections and, less frequently, PTLDs were associated with HSCT. Associations of orofacial granulomatosis-like lesions and oral mucosa-associated lymphoid tissue-type lymphoma with SOT, and of pyogenic granuloma and hairy leukoplakia with HSCT were unclear. Periodontal disease and dental caries were not associated with SOT/HSCT. For none of the local treatments was there a strong evidence of effectiveness. CONCLUSIONS: Solid organ transplant/HSCT recipients are at risk of orofacial diseases. Adequate management of these patients alleviates local symptoms responsible for impaired eating, helps prevent systemic and lethal complications, and helps where dental healthcare has been neglected.

Gender differences in oral manifestations among HIV-infected Brazilian adults.

AIM: The purpose of this study was to compare gender differences in the prevalence of oral lesions in HIV-infected Brazilian adults. METHODOLOGY: A retrospective study was conducted of medical records from HIV/AIDS patients from 1993 to 2004. Oral lesions were only included in this study if definitively diagnosed through microscopic analysis, therapeutic test or according to EC-Clearing house criteria. RESULTS: A total of 750 men and 237 women were included in the study. Statistically significant differences were observed only for oral hairy leukoplakia, Kaposi sarcoma and lymphadenopathy (P < 0.01). However, a model of logistic regression showed that only oral hairy leukoplakia presented a significant association with gender and males had a significantly likelihood (four times higher than females) of presenting with this oral manifestation [OR 4.3 (95% CI: 1.39-13.36)]. CONCLUSION: These data shows that oral manifestations are less prevalent in females than in males, particularly oral hairy leukoplakia.

[HIV infection in a patient with a referral diagnosis of sore throat].

HIV infection was documented in a patient with hairy leukoplakia and oral candidiasis who had the wrong referral diagnosis of sore throat in the absence of dental complaints. Dental treatment at an infectious hospital led to regression of oral mucosa lesions, but failed to arrest the progress of severe pneumonia presumably caused by a specific pathogen.

The advantages of oral cytopathology in the early diagnosis of HIV/AIDS: three case reports.

Oral lesions are common in human immunodeficiency virus (HIV)-infected patients, which may indicate impairment of the patient's general health status, and, in many cases, the oral lesions are the first sign of an HIV infection. Oral hairy leukoplakia (OHL) is a benign lesion of the oral mucosa related to Epstein-Barr virus (EBV) observed in HIV-positive individuals. The aim of this study was to report the contribution of oral cytopathology in the investigation of the HIV/AIDS status of patients as well as in the clinical and subclinical identification of OHL. Three patients were referred to the Oral Medicine Clinic in 2010. The patients were submitted to oral examination, and scrapes of the tongue were obtained. The Papanicolaou staining technique was used, and cytopathological analysis showed nuclear changes corresponding to cytopathic effects of EBV epithelial infection and candidiasis. The final diagnosis was OHL and candidiasis. Based on cytopathological diagnosis, an HIV serologic test was requested which revealed positive HIV serology. None of the patients was aware of their HIV serological status, and thus the cytopathology, by identifying OHL, contributed to the early diagnosis of HIV/AIDS. Cytopathology should be used as a routine procedure and it may be the method of choice for clinical and subclinical OHL diagnosis.

Common tongue conditions in primary care.

Although easily examined, abnormalities of the tongue can present a diagnostic and therapeutic dilemma for physicians. Recognition and diagnosis require a thorough history, including onset and duration, antecedent symptoms, and tobacco and alcohol use. Examination of tongue morphology and a careful assessment for lymphadenopathy are also important. Geographic tongue, fissured tongue, and hairy tongue are the most common tongue problems and do not require treatment. Median rhomboid glossitis is usually associated with a candidal infection and responds to topical antifungals. Atrophic glossitis is often linked to an underlying nutritional deficiency of iron, folic acid, vitamin B12, riboflavin, or niacin and resolves with correction of the underlying condition. Oral hairy leukoplakia, which can be a marker for underlying immunodeficiency, is caused by the Epstein-Barr virus and is treated with oral antivirals. Tongue growths usually require biopsy to differentiate benign lesions (e.g., granular cell tumors, fibromas, lymphoepithelial cysts) from premalignant leukoplakia or squamous cell carcinoma. Burning mouth syndrome often involves the tongue and has responded to treatment with alpha-lipoic acid, clonazepam, and cognitive behavior therapy in controlled trials. Several trials have also confirmed the effectiveness of surgical division of tongue-tie (ankyloglossia), in the context of optimizing the success of breastfeeding compared with education alone. Tongue lesions of unclear etiology may require biopsy or referral to an oral and maxillofacial surgeon, head and neck surgeon, or a dentist experienced in oral pathology.

[Progress on study on oral lesions in patients with AIDS].

A large number of studies showed that hairy leukoplakia, pseudomembranous candidiasis, Kaposi' sarcoma, non-Hodgkin's lymphoma, linear gingival erythema, necrotizing ulcerative periodontitis and necrotizing ulcerative gingivitis were the most common lesions in patients with HIV infection and AIDS, and their higher prevalence and incidence rates correlated with the falling CD4 counts and higher virus load of the patients. The use of highly active antiretroviral therapy (HAART) was associated with decreases in the prevalence of oral diseases. Oral manifestations may represent early signs of AIDS disease and call attention to disease progression. Oral fluid has been shown to possess superior sensitivity for HIV antibody detection as serum.

Identification of oral candidosis, hairy leukoplakia and recurrent oral ulcers as distinct cases of immune reconstitution inflammatory syndrome.

Oral lesions such as candidosis, hairy leukoplakia (HL) and oral ulcers are strikingly absent in the numerous reports of immune reconstitution inflammatory syndrome (IRIS). To document oral manifestations attributable to immune reconstitution, we conducted a longitudinal follow-up of a cohort of HIV+ individuals starting highly active antiretroviral therapy (HAART) and completing oral pathology follow-up up to 12 weeks after treatment initiation. HIV-infected patients had oral examinations, CD4+ T-cell count and viral load determinations performed at baseline, and at weeks 4, 8 and 12 after HAART initiation. Among individuals with satisfactory viral response and recovery of > or =50 CD4+ T-cell/microL, eight patients complied with strict IRIS criteria: two developed clinical signs of oral candidosis (OC), two oral ulcers, three HL and one Kaposi's sarcoma. CD4+ T-cell counts at symptom onset suggested no remaining immune suppression. Our findings show that cases of OC, HL and recurrent ulcers can be instances of IRIS.

Systematic review of the changing pattern of the oral manifestations of HIV.

The purpose of the present study paper was to review the reported prevalence of the oral manifestations of HIV (OM-HIV) worldwide since 1980, and to determine the global variation in its prevalence over time. PubMed, Scopus, Embase and Google Scholar were searched. The filter "English" was used. The timeframe searched was 1980- 2015. The PRISMA flow chart was used. Data were extracted using the Joanna Briggs Institute standardized data extraction form and transferred to SPSS version 22 for analysis. The systematic review of 97 studies (70 low bias risk) showed that the prevalence of OM-HIV continue to be significant in developing countries. Globally and through all the decades, oral candidiasis remained the most commonly encountered OM-HIV, including among patients on antiretroviral therapy (ART) (26.2%). Hairy leukoplakia was more prevalent in Europe and America compared with Africa and Asia. Oral warts were reported more often in studies on patients receiving ART. Interestingly, salivary gland disease decreased in the developed world and increased in developing countries over time. Despite the changing pattern of these conditions over time, there is no evidence that the OM-HIV have become of less significance globally. Maintaining the drive for high-quality research in the subject will have an impact on less developed countries to help address oral health inequalities.

HIV-related oral lesions, demographic factors, clinical staging and anti-retroviral use.

BACKGROUND: The aim of the present study was to compare the prevalence of HIV-related oral lesions (HIV-OL) between two health centers for HIV in Mexico City and to analyze the factors that, in addition to combined antiretroviral therapy (CART) and low CD4(+), may be associated with possible differences in prevalence. METHODS: A cross-sectional observational study was performed between January 2000 and February 2003 at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), a specialized referral center for HIV/AIDS patients and the Clínica Especializada Condesa (CEC), a primary care center for HIV-infected individuals without social security insurance. A consecutive sample of HIV-infected individuals had an oral examination based on established clinical criteria. Demographic, clinical and laboratory data were obtained. Independent association of each factor with specific HIV-OL was assessed by logistic regression modeling. RESULTS: Eight hundred fifty individuals were examined (INCMNSZ: 479; CEC: 371). Hairy leukoplakia (HL), periodontal disease (PD) and Kaposi's sarcoma (KS) were independently associated with the study site [odds ratio (OR) = 1.7 (95% confidence interval (CI): 1.1-2.4), OR = 4.2 (95% CI: 1.3-13), OR = 10.1 (95% CI: 2.7-38.2), respectively], being more frequent in CEC patients. HL was independently associated with men having sex with men OR = 1.7 (95% CI: 1.1-2.8). All HIV-OL were independently associated with CD4(+) counts and, with the exception of PD and KS, with time under CART. CONCLUSIONS: The present comparative study showed that several factors were associated with a difference in prevalence of oral lesions found in two AIDS clinics located in Mexico City. Severe immune suppression, CART duration and the study site were associated with HIV-OL. Further investigation into factors such as socioeconomic determinants associated with HIV-OL is warranted.

Oral lesions in Brazilian HIV-infected children undergoing HAART.

INTRODUCTION: The advent of new antiretroviral drugs such as protease inhibitors (PI) has generated sensible changes in oral manifestation patterns in human immunodeficiency virus (HIV) infected adult patients. OBJECTIVES: The purpose of the present study was to assess whether the use of highly active antiretroviral therapy (HAART) has brought changes to pattern and prevalence of oral lesions related to HIV in the HIV-infected pediatric population. CASUISTIC AND METHOD: We analyzed medical charts of 471 children aged zero to 12 years and 11 months with HIV infection and followed up by the Ambulatory of AIDS, Clinical Otorhinolaryngology, Hospital das Clinicas, Medical School, Sao Paulo University, from January 1990 to December 2004. Four hundred and fifty-nine children were divided into two groups, according to age range: X (0-5 years and 11 months) and Y (6-12 years and 11 months). These groups were subdivided into four subgroups, according to use of ART (antiretroviral therapy without PI) or HAART. We recorded data related to type of oral lesion presented, as well as serum CD4+ lymphocyte count. The groups were compared concerning prevalence and presentation pattern of oral manifestations. RESULTS: Out of 459 children, 144 (31.4%) had oral lesions. We observed that in children aged 6-12 years and 11 months who were taking HAART, there was lower prevalence of oral lesions (p=0.005), specially hairy leukoplakia (p<0.02), without any affection to the common presentation pattern of these lesions. The same subgroup also had higher serum CD4+ lymphocyte counts (p<0.001). CONCLUSION: We concluded that use of HAART could lead to reduction in prevalence of oral lesions in HIV-infected children.

Retrospective analysis of the clinical behavior of oral hairy leukoplakia in 215 HIV-seropositive patients.

Oral manifestations are common findings in human immunodeficiency virus (HIV) infected patients and frequently influence the overall health. Oral hairy leukoplakia (OHL) is strongly associated with HIV infection demonstrating its relationship with the individual's immune status and progression of immunosuppression. This study aims to retrospectively evaluate OHL in HIV patients, analyzing its incidence, demographic aspects and possible changes in clinical and epidemiological profile of the disease over 17 years. The records of 1600 HIV-infected patients were reviewed. The data were correlated and analyzed, considering HIV exposure category, age, gender, harmful habits, CD4 level, use and type of antiretroviral. OHL was observed in 215 (13.4%) patients. Most were men in the fourth decade of life, 171 (79.5%) and 112 (52,1%) respectively, but an increase in the incidence of OHL among female patients and those in the fifth decade of life was observed. Tobacco smoking was the most frequent harmful habit reported by 114 (68%) patients. OHL occurred mostly in patients with CD4 counts between 200 and 500 cells/mm3 35 (55.5%). The lower incidence of OHL was found among patients using at least one non-nucleoside reverse transcriptase inhibitor (NNRTI). OHL is related to CD4 count, use of ARVT and tobacco smoking and is also more prevalent in men in the fourth decade of life. These characteristics were recognized in absolute values, but when verifying the behavior over the years we noticed that the incidence of OHL is decreasing and its epidemiological characteristics changing.

Oral manifestations of HIV disease.

HIV-related oral conditions occur in a large proportion of patients, and frequently are misdiagnosed or inadequately treated. Dental expertise is necessary for appropriate management of oral manifestations of HIV infection or AIDS, but many patients do not receive adequate dental care. Common or notable HIV-related oral conditions include xerostomia, candidiasis, oral hairy leukoplakia, periodontal diseases such as linear gingival erythema and necrotizing ulcerative periodontitis, Kaposi's sarcoma, human papilloma virus-associated warts, and ulcerative conditions including herpes simplex virus lesions, recurrent aphthous ulcers, and neutropenic ulcers.

Synchronous kinetics of CD4+ lymphocytes and viral load before the onset of oral candidosis and hairy leukoplakia in a cohort of Mexican HIV-infected patients.

An observational, prospective, longitudinal cohort study was performed at the AIDS Clinic of a tertiary care institution in Mexico City to determine the association of viral load (VL) and CD4+ lymphocyte kinetics with the development of oral candidosis (OC) and hairy leukoplakia (HL). Participants were HIV-infected adult subjects, without a history of or current OC or HL, not receiving HAART. Oral examinations were performed at baseline and every month for evidence of OC or HL; CD4+ and VL determinations were done at baseline, at 6-month intervals, when oral lesions were detected, and 2 months later. Affected subjects (OL group) by OC or HL had clinical intervals defined before (antecedent), during (concurrent), and after their development. In the nonaffected individuals (NA group), 6-month intervals were determined. Differences (changes) along the clinical and study intervals were calculated for CD4+ and VL. The median study time was 178 (range: 31-924) days; 99 patients were included. The 2-year cumulative incidence of either oral lesion was 54% (49.5% for OC and 33.2% for HL). In the OL group (31 patients) a progressive and continuous decrease of CD4+ was found in the antecedent interval followed by a significant increase in VL in the concurrent period. The NA group showed a significant fall in CD4+ by semester 3, without a significant rise of VL in the following semester. The effect of CD4+ remained significant in a multivariate analysis. This study has shown that the onset of OC and/or HL is heralded by the sequence of a sustained reduction of CD4+, followed by a sharp increase of VL. In the multivariate analysis, the decrease in CD4+ lymphocytes appeared to be the predominant factor predicting the appearance of these oral lesions. Their potential use as markers of a recent change in the immunologic and virologic status of HIV-infected individuals is emphasized.

Longitudinal study of the prevalence and prognostic implications of oral manifestations in romanian children infected with human immunodeficiency virus type 1.

OBJECTIVE: We evaluated the prevalence and predictive value for human immunodeficiency virus (HIV) disease progression of oral manifestations in Romanian children. METHODS: A nonrandom sample of 238 HIV-infected children was followed prospectively between 1998 and 2001 at the Romanian-American Children's Center in Constanta, Romania. Study subjects underwent comprehensive annual oral examinations. Oral manifestations of interest, demographic data and other selected medical information were recorded at baseline and at each subsequent visit. Descriptive statistics and survival analysis methods were used in the study. A level of statistical significance of alpha = 0.05 was used. RESULTS: The study subjects' mean age was 9.9 +/- 1.2 (SD) years. The most common oral lesions were gingivitis (49%), parotid enlargement (13%) and oral candidiasis (11%). Oral candidiasis was associated with progression to acquired immunodeficiency syndrome or death (whichever occurred first) (log rank P = 0.03) and with death (log rank P < 0.001). Oral hairy leukoplakia also was associated with progression to death (log rank P = 0.001). The risk of dying was 3.43 (95% confidence interval, 1.86-6.34; P < 0.001) for children who had oral candidiasis at baseline and 4.62 (95% confidence interval, 1.67-12.77; P = 0.003) for those who had oral hairy leukoplakia. CONCLUSIONS: Oral manifestations occur commonly among HIV-infected Romanian children. Oral candidiasis and oral hairy leukoplakia were positive predictors of HIV disease progression.