Deborah Greenspan

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

We propose new classification criteria for Sjögrens syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.

ORAL "HAIRY" LEUCOPLAKIA IN MALE HOMOSEXUALS: EVIDENCE OF ASSOCIATION WITH BOTH PAPILLOMAVIRUS AND A HERPES-GROUP VIRUS

An outbreak of a new form of oral leucoplakia, found principally on the lateral borders of the tongue, is reported in male homosexuals in the San Francisco area. Many of the patients showed evidence of immunosuppression, and candida was often found in the lesions. The characteristic histology is similar to that of the flat wart of skin. There was immunocytochemical evidence of papillomavirus core antigen in 77% of 30 biopsy specimens, but no papillomaviruses were detected by electron microscopy in samples from 6 randomly selected patients. In 5 of these 6 patients there was evidence of a herpes-type virus. Pneumocystis carinii pneumonia has developed in 8 of 37 patients in a 33-month period. This leucoplakia may presage AIDS, may be associated with both papillomavirus and a herpes-type virus, and may offer clues to the pathogenesis of other forms of oral epithelial hyperplasia and dysplasia.

Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population

Human herpesvirus-6 (HHV-6) was recovered at high frequency (greater than 85%) from the saliva of both healthy individuals and those infected with the human immunodeficiency virus (HIV). The level of isolation mirrored the high prevalence of antibodies to HHV-6 found in sera obtained from residents of diverse areas of the world. Seroconversion occurred between 1 and 3 years of age; seroprevalence ranged between 80% and 100% among adults under 40 and decreased to 35% between ages 62 and 88. Serum titres in healthy individuals remained stable during periods of virus shedding. Immune cellular dysfunction in patients was associated with high geometric mean HHV-6 antibody titres. These observations suggest that HHV-6 infection takes place within the first 3 years of life, and strongly implicate oral shedding as a common means of transmission of this newly described herpesvirus.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men : three San Francisco epidemiological cohorts

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, Kaposis 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 (CD 17.5–23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% Cl 4.1–7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposis sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P < 0.05). The prevalence of erythematous candidiasis and Kaposis sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Osteonecrosis in patients irradiated for head and neck carcinoma.

One hundred patients irradiated for cancers of the oral cavity, oropharynx, and nasopharynx were evaluated for the occurrence of osteonecrosis and associated predisposing factors. Selection was based on availability of complete dental records, a minimum of six months follow‐up, and treatment fields, which included maxilla and/or mandible. Bone doses were calculated by using radiotherapy treatment records, port films, and isodose distributions. Osteonecrosis developed in 19 of 78 dentulous patients and in 3 of 22 edentulous patients. The time of development of osteonecrosis varied; in 15 cases osteonecrosis occurred more than one year after treatment. The most important risk factor for the development of osteonecrosis was the radiation dose to bone, particularly in the less vascular mandible. Osteonecrosis developed in 85% of the dentulous patients and in 50% of the edentulous patients who received more than 7500 rads to the bone. None of the patients who received less than 6500 rads developed osteonecrosis. The risk was significantly greater when teeth were removed after therapy compared with those individuals with extractions before radiation or no extractions at all.

Effect of highly active antiretroviral therapy on frequency of oral warts

To investigate changes in the pattern of oral disease associated with highly active antiretroviral therapy (HAART), we assessed the frequency of these lesions in our clinic over 9 years. We retrospectively studied 1280 patients seen between July, 1990, and June, 1999, and related oral findings to medication use, immune function, and viral load. We found significant decreases in oral candidosis, hairy leucoplakia, and Kaposis sarcoma over time, but no change in the occurrence of aphthous ulcers. There was an increase in salivary-gland disease and a striking increase in warts: three-fold for patients on antiretroviral therapy and six-fold for those on HAART (p=0.01). This pattern of oral disease in a referral clinic suggests that an increase in oral warts could be occurring as a complication of HAART.

Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase.

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.

Differential Expression of Candida albicans Secreted Aspartyl Proteinase and Phospholipase B Genes in Humans Correlates with Active Oral and Vaginal Infections

The in vivo expression of Candida albicans secreted aspartyl proteinase (SAP1-SAP8) and phospholipase B (PLB1 and PLB2) genes was analyzed in 137 human subjects with oral and vaginal candidiasis or carriage. Total RNA was isolated from whole unstimulated saliva or vaginal swabs, and the expression of SAP1-8 and PLB1-2 was evaluated by reverse-transcriptase polymerase chain reaction using specific primer sets. A spectrum of SAP gene expression profiles was obtained from different C. albicans strains during symptomatic disease and asymptomatic carriage. SAP2 and SAP5 were the most common genes expressed during both infection and carriage. SAP1, SAP3, SAP4, SAP7, SAP8, and PLB1 expression was correlated with oral disease, whereas SAP1, SAP3, and SAP6-SAP8 expression was correlated with vaginal disease. Furthermore, SAP1, SAP3, and SAP8 were preferentially expressed in vaginal, rather than oral, infections. This study demonstrates the differential expression of the hydrolytic enzyme genes in humans and correlates the expression of specific Candida species virulence genes with active disease and anatomical location.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

ObjectiveThis study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DesignCohorts 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. ParticipantsOf 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 measuresWe 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. ResultsUsing 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 (CD, 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. ConclusionThe presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.