Oral manifestations of HIV infection.
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HIV Infections↗
Biomedical subjects
D Greenspan
Publications and source records attributed to D Greenspan.
Human immunodeficiency virus-related oral manifestations and gender. A longitudinal analysis. The University of California, San Francisco Oral AIDS Center Epidemiology Collaborative Group.
BACKGROUND: Because human immunodeficiency virus (HIV) infection affects an increasing number of women in the United States, we investigated the role played by gender in the occurrence of HIV-related oral conditions. METHODS: As part of a 4-year prospective study of 3 epidemiological cohorts, oral and physical examinations (including blood tests) were performed on HIV-infected men (n = 200) and women (n = 218) at 6-month intervals. Our outcome variables included oral conditions commonly associated with HIV infection: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin lymphoma, Kaposi sarcoma, and parotid enlargement. RESULTS: Only hairy leukoplakia, candidiasis, and ulcers were observed. The occurrence of hairy leukoplakia and candidiasis was higher in men (22% and 24%, respectively) than in women (9% and 13%, respectively) during the study period. A regression model for longitudinal data (generalized estimating equation) disclosed that the odds of having hairy leukoplakia were 2.5 times higher for men than for women, after controlling for CD4+ cell count, race, and injecting drug use (95% confidence interval, 1.34-4.76; P = .003). Length of follow-up did not confound this association. A weaker association was found between the occurrence of oral candidiasis and gender (adjusted odds ratio, 1.85; 95% confidence interval, 1.0-3.43; P = .05). CONCLUSIONS: In this sample of HIV-infected adults, we found that men were significantly more likely to have hairy leukoplakia than were women. The hairy leukoplakia-gender association merits further investigation, because it may be related to a gender difference in the mode of expression of Epstein-Barr virus.
Adult↗
HIV-related oral disease.
Few people with HIV infection fall to experience oral lesions during the course of their disease. Oral mucosal and salivary gland manifestations include several that were not seen before the AIDS epidemic, while others are more severe in this population. Oral lesions reflect HIV status and the stage of immunosuppression, are important elements in HIV staging and classification schemes, raise pertinent questions about mucosal aspect of immunosuppression, and provide therapeutic challenges. Their pervasive nature and biological significance emphasise the importance of a careful oral examination as part of the general clinical evaluation.
AIDS-Related Opportunistic Infections↗
Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis.
To determine whether daily use of nystatin pastilles can prevent initial outbreak or recurrence of oral candidiasis in HIV-infected patients and to identify factors associated with outbreaks during 20-week follow-up, a randomized, double-blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV-infected men (aged 27-60 years) who either had had no documented episode of oral candidiasis in the previous year or had been clinically clear of oral candidiasis for at least 72 h before randomization. Study arms were two placebo pastilles, one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles daily for 20 weeks. The main outcome measure was time to oral candidiasis, as determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate proportional hazards model showed that four factors were significant (p < 0.001) in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59), history of oral candidiasis (3.58), Candida albicans carriage (2.79), and CD4 count at randomization (0.65). In this small group of subjects, nystatin appeared to be effective in delaying onset of oral candidiasis. Patients with CD4 counts < 200 who are carriers of C. albicans and have a history of oral candidiasis may be most likely to benefit from antifungal prophylaxis.
AIDS-Related Opportunistic Infections↗
Novel HPV types present in oral papillomatous lesions from patients with HIV infection.
Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69.
Base Sequence↗
Sequence variation of latent membrane protein-1 of Epstein-Barr virus strains associated with hairy leukoplakia.
The Epstein-Barr virus (EBV) latent membrane protein (LMP)-1 is expressed in hairy leukoplakia (HL), but data on LMP-1 sequence variation of HL isolates are limited. Variation in the LMP-1 repeat region and presence of a 30-nt deletion were studied using DNA scrapings from 28 HL lesions. cDNAs from 3 different HL isolates were sequenced, 2 from lymphocyte cell lines (LCLs) generated using HL biopsy material. The deletion was found in 16 (57%) of 28 HL scraping, and multiple repeat region variants were seen in 13 scrapings (46%). HL LMP sequence were similar to those described in nasopharyngeal cancer and lymphoma tissues, including two motifs of four amino acid changes relative to B95-8 upstream and downstream of the repeat region, respectively. Generation of LCLs using HL biopsy material confirmed the ability of HL EBV strains to infect and transform lymphocytes.
Amino Acid Sequence↗
Apoptosis-associated proteins in oral hairy leukoplakia.
OBJECTIVE: To test the hypothesis that the anti-apoptotic ability of Epstein-Barr virus (EBV) may result in altered expression of apoptosis-associated proteins in oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for these proteins by immunohistochemistry. MATERIALS AND METHODS: Twenty formalin-fixed, paraffin-embedded specimens of HL lesions and six specimens of normal control mucosa were selected from archived tissue specimens. Bcl-2, Bcl-x, Bax and p53 apoptosis-associated proteins were evaluated in immunohistochemically stained tissue sections according to staining intensity and pattern. The percentage of p53-positive basal cells was estimated in sequential fields. RESULTS: Generally, there were only slight differences in the expression of Bcl-2 and Bcl-x proteins in the epithelium of HL and control tissue. The staining for Bcl-2 was weaker in keratinocytes than in putative melanocytes and Langerhans cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted. Keratinocytes throughout the epithelium stained positively for Bcl-x protein, although upper layers were more weakly stained. The 'balloon' keratinocytes in HL were infrequently positive for Bcl-x. Bax staining in HL differed from that in control tissue in being more heterogeneous. The staining reaction in HL was weak to negative in upper epithelial levels where 'balloon' keratinocytes were located. Weak to moderate nuclear p53 protein staining was detected in a mean of 25.3% of basal keratinocytes in all but one of the HL specimens; weak staining was seen in only two control specimens. CONCLUSIONS: We found only slight immunohistochemical evidence that expression of the apoptosis-associated proteins is altered in HL. p53 appears to over-expressed in HL; we speculate that this may be related to up-regulation or stabilization of wild-type p53 protein related to EBV infection.
Adult↗
Expression of laminin 5, fibronectin, and epithelium-associated integrins in recurrent aphthous ulcers.
Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate.
Adult↗
Xerostomia: diagnosis and management.
Xerostomia, or dry mouth, is a common complaint that may be caused by several conditions, which include side effects of a wide variety of drugs, such as antidepressants, therapeutic radiation to the head and neck, dehydration, diabetes, and diseases involving salivary glands, such as Sjögren's syndrome. The complaint of dry mouth may or may not be associated with decreased salivary gland function. Individuals with xerostomia complain of problems with eating, speaking, swallowing, and wearing dentures. Some people also complain of salivary gland enlargement or changes in taste. Lack of saliva may predispose one to oral infections, such as candidiasis, and increase the risk of dental caries. Management of the individual patient with xerostomia includes assessment of salivary gland function, replacement therapy, and prevention of caries and oral candidiasis. Early recognition and management of xerostomia may prevent devastating dental disease and help to improve the quality of life.
Antidepressive Agents↗
Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy.
PURPOSE/OBJECTIVES: To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF: Mouth Aware (PSMA)-in conjunction with two mouthwashes (0.12% chlorhexidine or sterile water) in preventing chemotherapy-induced oral mucositis. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTINGS: 23 outpatient clinics and office practices in California. SAMPLE: 222 patients who were starting a cycle of mucositis-inducing chemotherapy. METHOD: Participants were followed over three chemotherapy cycles. All patients were provided the PSMA program. Random assignment to a mouthwash occurred prior to the development of oral mucositis. Researchers used the Oral Assessment Guide to assess the patients oral cavities monthly (with the patients cycles of chemotherapy) and when patients reported any oral changes between cycles. MAIN RESEARCH VARIABLES: Type of mouthwash, incidence, days to onset, and severity of chemotherapy-induced oral mucositis. FINDINGS: No significant differences existed between the two mouthwashes in regard to incidence, days to onset, and severity of mucositis. CONCLUSIONS: Because chlorhexidine (S20 per pint) was no more effective than water, a substantial cost savings can be realized by rinsing with water. Interestingly, the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44% to less than 26%. IMPLICATIONS FOR NURSING PRACTICE: A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis.
Adult↗
Herpetic gingivostomatitis in a 70-year-old man.
We report a case of herpetic gingivostomatitis that was remarkable because it occurred in a 70-year-old man. The patient had multiple small ulcers throughout the mouth that were culture-positive for herpes simplex virus type 1 and responded rapidly to acyclovir. Whether this condition was a case of primary herpes or an unusual presentation of secondary disease was not resolved. Nevertheless the case serves as a reminder that age, although it may make a diagnosis seem implausible, does not alone exclude it.
Acyclovir↗
Direct immunofluorescence vs. culture for detecting HSV in oral ulcers: a comparison.
Diagnostic tests may be necessary to determine the cause of oral ulcers. Direct immunofluorescence staining of oral smears supplies results much more quickly than viral culture, the "gold standard" for diagnosing HSV lesions. This study compares the sensitivity and specificity of direct immunofluorescence staining vs. viral culture and evaluates the usefulness of the two techniques for the general dental practitioner.
Adolescent↗
Treatment of oral candidiasis in HIV infection.
Oral candidiasis is one of the most common clinical features of HIV infection. The lesion occurs in three predominant forms, and the two intraoral examples, pseudomembranous and erythematous, are equally predictive of the development of AIDS, independent of CD4 counts. The predominant species is C. albicans, although other species are occasionally found. Some studies claim correlation of salivary Candida counts with CD4 numbers or clinical stage of HIV-related disease, but this approach has not been used widely in HIV staging. Therapy with a variety of antifungal agents, including both topical and systemic drugs, is effective. New slow-release oral topical drug delivery systems may prove to be useful. Recently, examples of resistance to some drugs have been reported. Resistance may be associated with the emergence of different species.
AIDS-Related Opportunistic Infections↗
Treatment of oropharyngeal candidiasis in HIV-positive patients.
Most HIV-positive patients develop some form of oral candidiasis, most commonly pseudomembranous candidiasis, erythematous candidiasis, or angular cheilitis, at some point in their disease. All these manifestations are important risk markers for disease progression. Oral candidiasis is generally caused by Candida albicans. Although oral candidiasis can occur at any stage of HIV infection, it is most common in patients with low CD4 counts. Numerous oral and systemic therapies are used to treat oral candidiasis, the most popular of which are nystatin (topical), clotrimazole (topical), ketoconazole (systemic), fluconazole (systemic), and itraconazole (systemic). The topical agents are available in assorted dosage forms with varying degrees of efficacy and patient acceptability. The limited data currently available suggest an advantage for the systemic agents, although problems with resistance may limit the usefulness of fluconazole. The efficacy, safety, and cost effectiveness of a given agent must be considered when prescribing a specific agent for the treatment of oral candidiasis.
Administration, Oral↗
HPV-associated epithelial atypia in oral warts in HIV+ patients.
Reported are oral mucosal warts (HPV common antigen-positive) from 7 adult HIV+ patients in which there was cytologic atypia and disordered growth. Lesions were papillary, white to red in color, and were located on the lip, gingiva, palate, tongue, and buccal mucosa. Histologically, the keratinocytes in the lesions exhibited atypical features in the form of hyperchromatism and karyomegaly. Koilocytes were frequently seen in the upper level keratinocytes where HPV common antigen was identified. The dysplastic areas, which ranged from mild to severe, typically showed abrupt limiting margins. All lesions exhibited intense PCNA reactivity from basement membrane to surface. Nuclei of mid-level and basal keratinocytes of 3 specimens stained positively for p53 protein. We believe that the atypia found in these lesions represents cytologic change that has malignant potential. The subtype of the HPV in these lesions has not yet been determined.
Adult↗
HIV-related oral manifestations in two cohorts of women in San Francisco.
The goals of this study were to compare the prevalence of oral lesions in women infected with human immunodeficiency virus (HIV) and HIV-negative women, and to determine the association of oral lesions with route of HIV transmission and with level of immunosuppression in infected women. As part of a prospective 4-year study, oral examinations and blood tests were performed, at 6-month intervals, on 176 HIV-infected women and on 117 HIV-negative women at risk for HIV infection. We evaluated participants for the following oral conditions: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin's lymphoma, Kaposi's sarcoma, and parotid enlargement. As previously reported in men, the prevalence of oral lesions was significantly higher among HIV-infected (22%) than HIV-negative women (3%) [odds ratio (OR) = 8.2; 95% confidence interval (CI) 2.8, 23.5], particularly candidiasis (14%) and hairy leukoplakia (10%). Among HIV-infected women with CD4 cell count nadir > or = 200 cells/microliters, the prevalence of hairy leukoplakia was higher among those infected heterosexually than among injection drug users (OR = 5.5; 95% CI: 1.5; 19). The OR for the association between oral lesions and CD4 cell count nadir (< 200 vs. > 500 cells/microliters) was 8.9 (95% CI: 2.6, 30), indicating a strong positive association with level of immunosuppression.
Adult↗
The mouth in human immunodeficiency virus infection.
Oral manifestations are a common feature of human immunodeficiency virus (HIV) infection. They may present as neoplasms, opportunistic infections, or other lesions. The dermatologist may be the first health care provider to suspect HIV infection when recognizing some of the oral lesions described in this article. Some of these lesions may be of prognostic significance for the subsequent development of AIDS. Management of the oral lesions can significantly reduce morbidity and improve quality of life.
AIDS-Related Opportunistic Infections↗
Multi-focal oral non-Hodgkin's lymphoma in an AIDS patient.
Cases of non-Hodgkin's lymphoma (NHL) occurring in immunosuppressed patients, including those who are infected with the human immunodeficiency virus, may develop in areas other than the lymph nodes. In AIDS-associated NHL, about 5% of cases of extranodal NHL are intra-oral. This case report describes the presentation of malignant non-Hodgkin's lymphoma in the mouth of a man who had AIDS. The lesion arose on separate occasions at three distinct sites, spontaneously regressing at each site prior to appearing at another intra-oral site.
Adult↗