Xerostomia associated with didanosine.
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Biomedical subjects
Publications and source records attributed to D Greenspan.
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Infections with Geotrichum species, although rare, are sometimes seen in immunocompromised hosts. We report a case of oral geotrichosis in a patient seropositive for human immunodeficiency virus who had erythematous mandibular and maxillary gingiva but was otherwise free of any active systemic disease. Geotrichum candidum was shown by both culture and histopathology to be present in the lesion and was deduced to be the causative organism. The patient responded well to several weeks of treatment involving oral topical administration of nystatin vaginal tablets.
To describe the natural history of HIV-associated salivary gland disease, which is characterized by enlarged major salivary glands and/or xerostomia in HIV-infected persons, we assessed 22 patients at an initial and follow-up examinations (median span of examinations, 15 months). Sixteen patients (73%) had bilateral parotid gland enlargement, 17 had symptoms of dry mouth, and 11 had both conditions. Parotid gland enlargement remained unchanged in 10 patients, it progressed in 2, and it regressed in 4 during treatment with zidovudine or steroids. Those patients with parotid gland enlargement had a significantly lower mean stimulated parotid flow rate (0.27 ml/min/per gland) than a control group of HIV+ persons without salivary gland disease (0.48 ml/min/per gland) (p less than 0.05), whereas the mean unstimulated whole salivary flow rates did not did not differ significantly between the two groups. The mean salivary flow rate of the study group did not change during the observation period. When HIV-associated salivary gland disease was diagnosed, 5 patients (23%) had AIDS, and at follow-up 10 (46%) had AIDS. Seven of these had Kaposi's sarcoma. The mean peripheral blood CD4 cell count was 280 and 225 per mm3 at the initial and follow-up examinations, respectively. The corresponding CD8 counts were 1138 and 900. The pathogenesis of HIV-associated salivary gland disease may include hyperplasia of intra-parotid lymphoid tissue. Because HIV-associated salivary gland disease can clinically resemble Sjögren's syndrome, the differential diagnosis of bilateral parotid enlargement should include HIV infection.
In 4.4% of human immunodeficiency virus-associated non-Hodgkin's lymphoma the presenting lesion is seen in the mouth. Often the lesion may clinically resemble a less sinister process, and a definitive diagnosis of lymphoma may be delayed. We describe three unusual cases of non-Hodgkin's lymphoma, appearing intraorally in association with other oral lesions, in HIV-positive homosexual men. The three patients reported here were all diagnosed as having diffuse, large-cell malignant non-Hodgkin's lymphoma. We performed Epstein-Barr virus DNA in-situ hybridization on our cases and Epstein-Barr virus DNA sequences were not seen. We review the pertinent literature and stress the importance of including non-Hodgkin's lymphoma in the differential diagnosis of oral lesions in patients at risk of HIV infection.
Recurrent aphthous ulcers in patients with HIV infection can cause significant morbidity, which makes successful diagnosis and treatment imperative. We have found that the diagnostic paradigm for recurrent aphthous ulcers in HIV-seronegative patients, which is based on the ulcers' clinical appearance, location, absence of other ulcer-causing pathogens or pathogenic processes, and response to therapy, may be successfully applied to recurrent aphthous ulcers in HIV-infected patients. However, one must be alert for ulcers with uncommon causes as well as ulcers with common causes that have atypical clinical appearances that may mimic recurrent aphthous ulcers. The topical glucocorticoids, which are used to treat recurrent aphthous ulcers in HIV-seronegative patients, proved very effective in HIV-infected patients for treatment of herpetiform and minor ulcers and most major ulcers and were without notable side effects. A few severe cases of major recurrent aphthous ulcers required treatment with systemic prednisone, and some side effects were encountered.
Since the original description of oral hairy leukoplakia among homosexual men in San Francisco in 1984, this white lesion of the tongue has been seen in the mouths of persons infected with the human immunodeficiency virus (HIV) worldwide. Its presence in HIV-positive persons usually but not always indicates fairly rapid progression to acquired immunodeficiency syndrome in the absence of antiretroviral therapy. Although the lesion appears to be common in HIV-positive persons, it is also, albeit rarely, seen in other conditions associated with immunosuppression. Epstein-Barr virus is associated with and presumably causes hairy leukoplakia, and the lesion offers insights into the biology of this ubiquitous DNA-oncogenic virus.
OBJECTIVE: This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN: Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS: Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES: We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS: Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION: The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.
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The fungus Histoplasma capsulatum causes histoplasmosis, the most common endemic respiratory mycosis in the United States. Disseminated histoplasmosis in adults is often associated with immunosuppression, such as occurs in HIV infection. We report a case of oral histoplasmosis in an HIV-seropositive patient who presented with an ulceration on the left tip of the tongue, extending to the floor of the mouth, but was otherwise free of any active systemic disease. Histoplasma capsulatum was shown, by both histopathology and staining with a fluorescent antibody reagent specific for the organism, to be present in the lesion and was deduced to be the causative organism.
Restriction fragment polymorphism analysis was used to investigate the identity and genotypic relatedness of Candida albicans strains isolated from human immunodeficiency virus (HIV)-infected patients with or without oral candidiasis and from some of their sexual partners. Use of the species-specific DNA probe Ca3 revealed that most subjects carried a single distinct C. albicans strain throughout the course of the study, during both symptomatic and asymptomatic periods. Sexual partners were more likely to carry the same or similar C. albicans isolates than unrelated subjects, raising the possibility of transmission via intimate contact. One patient appeared to acquire his partner's isolate, which then became predominant in both partners in subsequent isolations. These findings indicate that recurrent oral candidiasis is usually caused by a single persistent strain unique to each patient, but that in some cases transmission via intimate contact may occur between sexual partners.
Human immunodeficiency virus (HIV) associated salivary gland disease is defined as the presence of enlargement of one or more major salivary glands and/or diminished salivary function in an HIV infected individual. It has a number of similarities to, as well as differences from, Sjögren's syndrome (SS). We studied the sialochemistry of stimulated parotid saliva of 11 patients with HIV associated salivary gland disease and bilateral parotid gland enlargement, and compared these findings with those of 15 HIV negative controls, 13 HIV positive individuals with no salivary gland involvement and 18 individuals with SS. The patients with HIV associated salivary gland disease had a significant decrease in the level of salivary protein, with increases in salivary IgA, lysozyme and albumin compared to the HIV negative controls. There were no changes in concentration of electrolytes. The sialochemistry among the patients with HIV associated salivary gland disease was unrelated to the degree of immune suppression and did not change over a 6 month period. The observed changes were similar to those of SS but less pronounced. The similar clinical, histologic and sialochemical features of HIV associated salivary gland disease and SS suggest that these conditions share common pathogenetic mechanisms, which may be modified in the former by the HIV infection.
We investigated the prevalence of HIV-associated periodontal disease in an AIDS clinic in San Francisco. Patient recruitment occurred over 6 months with 90% patient participation. In 136 patients, three forms of periodontal disease were recorded: HIV-associated gingivitis (HIV-G), HIV-associated periodontitis (HIV-P), and conventional non-HIV-associated periodontal disease. Diagnosis was based on defined clinical criteria established before the study began. For the HIV-associated diseases, two sets of diagnostic criteria were used. One consisted of clinical signs that included bleeding on probing, pocket depth, and attachment loss; and the other consisted of the same signs but did not require probing (the measurement of the depth of the gingival sulcus). Using the first set of these criteria, HIV-G was diagnosed in 42 patients [31%; 95% confidence interval (CI) 23 to 39%] and HIV-P in 5 (4%; 95% CI 1 to 7%). Using the second set, 68 patients were diagnosed with HIV-G (50%; 95% CI 42 to 58%) and 8 with HIV-P (6%; 95% CI 2 to 10%). All other categories of periodontal disease that were non-HIV-associated were diagnosed in 60 (44%) of patients. These results indicate that while the prevalence of HIV-P is low, the prevalence of HIV-G and conventional periodontal disease among HIV-infected individuals is high and should be considered in the dental care of these patients.
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This study was conducted to characterize the recurrent aphthous ulcers (RAU) found in association with human immunodeficiency virus (HIV) infection, to examine evidence for increased severity of the ulcers with HIV disease, and to determine whether increased severity is associated with abnormalities of peripheral blood lymphocyte subsets. Seventy-five HIV-seropositive patients with RAU were followed for up to 2 years, and lymphocyte subsets were analyzed in 42. Minor, herpetiform, and major ulcer types were seen, but unexpectedly, 66% of the patients had the usually uncommon herpetiform and major types. These types were temporally associated with symptomatic HIV disease. Patients with major RAU were significantly more immunosuppressed than those with minor or herpetiform RAU in that they had fewer CD4 and CD8 lymphocytes (p less than 0.05). The lesion of RAU is considered to represent a local breakdown in immunoregulation. The systemic immune imbalance seen with HIV disease may amplify the local defect and lead to more severe ulcers.
A study of subject compliance within an experimental anti-HIV drug protocol was conducted with 40 asymptomatic HIV seropositive persons participating in a double-blind, placebo controlled trial of the effectiveness of ZDV. Subject compliance was assessed through the use of study nurse independent ratings. The 20 most compliant and 20 least compliant subjects were surveyed at a 6-month interval using a self-report instrument designed to assess perceived social support and other psychosocial factors thought to effect compliance. Results indicated that more adherent subjects lived further from their treatment site, did not live alone, saw their study nurse as supportive, and were more likely to depend on a significant other for a wide range of social, economic, and emotional support. Implications for the practical use of these findings are discussed and suggestions for future research are proposed.
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To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.
Epstein-Barr virus (EBV) infects both B lymphocytes and oropharyngeal epithelium, and it has been argued that the true reservoir of virus persistence in vivo is the self-renewing basal epithelial compartment. The identification of oral hairy leukoplakia (HL) of AIDS patients as a clinically apparent focus of EBV replication in lingual epithelium therefore provides a means of studying the EBV-epithelial cell interaction in situ. Replicative EBV DNA and productive cycle antigens are restricted to the upper, more differentiated epithelial layers in HL, and here we have applied highly sensitive in situ hybridization and immunohistological methods to examine the lower basal/suprabasal layers for evidence of latent EBV infection. We could not detect EBV DNA in these layers using an in situ DNA hybridization protocol which, on reference B cell lines, detected 1 viral genome/cell. Likewise, using sensitive in situ RNA hybridization for both the small non-polyadenylated EBER RNAs (abundant transcripts seen in all known forms of EBV latency) and the latent membrane protein (LMP) mRNA (the most abundant viral mRNA in B lymphoblastoid cell lines), the basal/suprabasal cells in HL were consistently negative; immunohistological staining with specific monoclonal antibodies also gave no evidence of latently infected LMP-positive cells. When the biopsy extracts were analysed by immunoblotting with selected human antisera, in addition to abundant productive cycle antigens, a band of constant size (66K) was observed which also reacted with immunopurified antibodies monospecific for one of the latency-associated nuclear antigens, EBNA 1; the cellular origin of this EBNA 1 could not be ascertained, but it is possible that in HL the protein is expressed during the productive cycle. The absence of demonstrable EBV latency in the basal/suprabasal cells of HL suggests that this is purely a virus replicative lesion which is sustained by continual re-infection of the maturing epithelium, not by the maturation of latently infected cells from the basal compartment.