Laurence Toutous-Trellu

Predicting the evolution of Kaposi sarcoma, in the highly active antiretroviral therapy era

Background:The outcome of Kaposi sarcoma varies. While many patients do well on highly active antiretroviral therapy, others have progressive disease and need chemotherapy. In order to predict which patients are at risk of unfavorable evolution, we established a prognostic score. Method:The survival analysis (Kaplan–Meier method; Cox proportional hazards models) of 144 patients with Kaposi sarcoma prospectively included in the Swiss HIV Cohort Study, from January 1996 to December 2004, was conducted.Outcome analyzed: use of chemotherapy or death.Variables analyzed: demographics, tumor staging [T0 or T1 (16)], CD4 cell counts and HIV-1 RNA concentration, human herpesvirus 8 (HHV8) DNA in plasma and serological titers to latent and lytic antigens. Results:Of 144 patients, 54 needed chemotherapy or died. In the univariate analysis, tumor stage T1, CD4 cell count below 200 cells/μl, positive HHV8 DNA and absence of antibodies against the HHV8 lytic antigen at the time of diagnosis were significantly associated with a bad outcome.Using multivariate analysis, the following variables were associated with an increased risk of unfavorable outcome: T1 [hazard ratio (HR) 5.22; 95% confidence interval (CI) 2.97–9.18], CD4 cell count below 200 cells/μl (HR 2.33; 95% CI 1.22–4.45) and positive HHV8 DNA (HR 2.14; 95% CI 1.79–2.85).We created a score with these variables ranging from 0 to 4: T1 stage counted for two points, CD4 cell count below 200 cells/μl for one point, and positive HHV8 viral load for one point. Each point increase was associated with a HR of 2.26 (95% CI 1.79–2.85). Conclusion:In the multivariate analysis, staging (T1), CD4 cell count (<200 cells/μl), positive HHV8 DNA in plasma, at the time of diagnosis, predict evolution towards death or the need of chemotherapy.

Assessment of a real-time PCR test to diagnose syphilis from diverse biological samples

Objectives: To investigate the contribution of a real-time PCR assay for the detection of Treponema pallidum in various biological specimens with the secondary objective of comparing its value according to HIV status. Methods: Prospective cohort of incident syphilis cases from three Swiss hospitals (Geneva and Bern University Hospitals, Outpatient Clinic for Dermatology of Triemli, Zurich) diagnosed between January 2006 and September 2008. A case–control study was nested into the cohort. Biological specimens (blood, lesion swab or urine) were taken at diagnosis (as clinical information) and analysed by real-time PCR using the T pallidum 47 kDa gene. Results: 126 specimens were collected from 74 patients with primary (n  =  26), secondary (n  =  40) and latent (n  =  8) syphilis. Among primary syphilis, sensitivity was 80% in lesion swabs, 28% in whole blood, 55% in serum and 29% in urine, whereas among secondary syphilis, it was 20%, 36%, 47% and 44%, respectively. Among secondary syphilis, plasma and cerebrospinal fluid were also tested and provided a sensitivity of 100% and 50%, respectively. The global sensitivity of T pallidum by PCR (irrespective of the compartment tested) was 65% during primary, 53% during secondary and null during latent syphilis. No difference regarding serology or PCR results was observed among HIV-infected patients. Specificity was 100%. Conclusions: Syphilis PCR provides better sensitivity in lesion swabs from primary syphilis and displays only moderate sensitivity in blood from primary and secondary syphilis. HIV status did not modify the internal validity of PCR for the diagnosis of primary or secondary syphilis.

Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study.

Background:Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis. Methods:Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form. Results:Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:≥32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer. Conclusion:Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

Traitement par cidofovir topique d'infections cutanées à papillomavirus humain, poxvirus et Herpes simplex virus chez des malades séropositifs pour le VIH

INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.

Increased incidence of sexually transmitted infections in Geneva, Switzerland.

Background: Focal outbreaks of sexually transmitted infections (STIs) such as syphilis and gonorrhoea have been reported in the large cities of Western Europe over the past few years. The aim of our study was to determine whether a similar trend is observed in Geneva and the situation with regard to HIV infection. Methods: We review the incidence of syphilis, gonorrhoea, Chlamydia trachomatis and HIV in Geneva from 1999 to 2004. Results: Figures indicate a steady and sustained increase in the incidence of syphilis, gonorrhoea and Chlamydia trachomatis in Geneva since 1999 that is maintained into 2004. As for HIV, the number of positive testings in Switzerland has stabilised and primary infection figures do not indicate an increase in newly acquired infections in Geneva. Conclusion: The situation in Geneva is similar to that observed elsewhere in Western Europe and indicates the need of public health interventions.

Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.

Performance of the 47-Kilodalton Membrane Protein versus DNA Polymerase I Genes for Detection of Treponema pallidum by PCR in Ulcers

ABSTRACT Treponema pallidum PCR (Tp-PCR) is a direct diagnostic method for primary and secondary syphilis, but there is no recommendation regarding the best choice of target gene. In this study, we sequentially tested 272 specimens from patients with sexually transmitted ulcers using Tp-PCR targeting the tpp47 and then polA genes. The two methods showed similar accuracies and an almost-perfect agreement.

Hyaluronic Acid Filler in HIV-Associated Facial Lipoatrophy: Evaluation of Tissue Distribution and Morphology with MRI

Objective: This prospective observational study evaluated magnetic resonance imaging (MRI) findings of hyaluronic acid (HA) injections used for the correction of HIV-associated facial lipoatrophy. Methods: Ten consecutive males underwent subdermal HA injection (mean 1.3 ± 0.6 ml per side) and MRI examinations prior to and then 1, 6 and 12 months after injection. Two radiologists blinded to the clinical data assessed morphologic and quantitative changes. Results: MRI revealed HA deposition in the subdermal and deep fat compartments. A significant HA volume increase was observed 1 month after injection (mean increase 331%, p < 0.0001) as compared to the injected amount. No volume reduction occurred at 12 months (p = 0.9961). The measured bound water content did not change (p > 0.9991), whereas skin thickness and tissue vascularization increased during the first 6 months (p = 0.01). Conclusion: Our data show that the cosmetic results of HA injections are caused by water binding in the deep facial fat and by a transient increase in vascularization and skin thickness.

Kaposi’s Sarcoma after Repeated Surgical Procedures in an Immunocompetent Patient: The Lymphatic Hypothesis

A 63-year-old Swiss patient developed acquired nodules on his right palm after 3 localized surgeries, called ‘needle fasciotomy’, for Dupuytren’s disease. Kaposi’s sarcoma (KS) was diagnosed in a biopsy of a nodule. A positive immunolabeling and serology for human herpesvirus 8 has been found, but human immunodeficiency virus and hepatitis C identification remained negative. The nodules were limited to the surgically traumatized area. This first report of a nonimmunocompromised patient developing a KS after repeated surgeries in a unique peculiar localized area with a dense lymphatic network sustains the hypothesis that tissue alterations involving the lymphatic system could play a central role in the occurrence of KS.

Three cases of cutaneous sarcoidosis: search for bacterial agent by the 16S RNA gene analysis and treatment with antibiotics.

Background: The aetiology of sarcoidosis remains controversial. An infectious origin is often discussed, but only anti-inflammatory or immunosuppressive treatment is recommended. Objectives: To investigate the hypothesis of bacterial origin by treating cutaneous sarcoidosis with antibiotics. Methods: Patients with chronic cutaneous sarcoidosis, unresponsive to the usual treatment and not requiring systemic corticotherapy, were given combined antibiotherapy for 6 months. Search for bacterial DNA by amplification and sequencing of the 16S ribosomal RNA gene in skin biopsies of lesions before and after antibiotherapy was done. Results: Three patients received a combined treatment with clarithromycin 1 g/day and ciprofloxacin 1 g/day. No clinical changes occurred in 2 cases and transient worsening in 1. Amplification for bacterial DNA was positive in all skin biopsies. The sequencing of this DNA could not identify a unique bacterial species. Conclusion: No evident bacterial origin could be demonstrated; however, this approach should be extended to more patients.