Marc Pechère

Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: A prospective pilot study

BACKGROUND Early studies using HIV protease inhibitors (PI) showed regression of Kaposis sarcoma (KS) lesions in some patients. OBJECTIVE Our purpose was to determine prospectively the influence of PI on HIV-related KS. METHODS KS lesions of nine patients with progressive cutaneous disease were prospectively evaluated clinically and by means of epiluminescence microscopy before and during PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS All patients experienced reduction or initial stabilization of KS lesions during the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months and according to AIDS Clinical Trials Groups criteria, six patients had a partial response, two showed stable disease, and in one noncompliant patient KS progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction in skin surface alterations, lesional size, and color intensity was demonstrated in six of nine patients. PI induced a median decrease in viremia of 1.66 log and a median increase in the CD4 count of 49 cells/mm3. CONCLUSION In this series, HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may result from the improvement in cellular immunity. These results suggest the use of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV viremia.

Red fingers syndrome in patients with HIV and hepatitis C infection

SIR—We observed a cutaneous sign involving the hands and feet of more than 1% of HIV-1 infected patients attending our clinic. Well-demarcated distal erythema of fingers and toes with multiple periungual telangiectasia were found in nine HIVinfected patients (figure). This symptom was permanent (eight of nine), painless (eight of nine), and there were no other complaints or Raynaud’s phenomenon. Median duration of symptoms was 9 months (range 0·5–90). All patients had abused intravenous drugs or alcohol. Laboratory data showed no antinuclear antibodies in eight (one patient had antibodies at a titre of 1/2560), normal muscle enzyme values (creatine kinase or aldolase) in seven of seven, and cryoglobulinaemia in three or three. Capillaroscopy examinations were normal (four of four) but histology showed dilated capillaries in the only skin biopsy specimen examined. Medications at the time of diagnosis were methadone (seven), benzodiazepines (six), co-trimoxazole (two), sulfadiazine/pyrimethamine (two), pentamidine (two), and zidovudine (one). Concomitant or previous opportunistic diseases were toxoplasmosis (two), disseminated mycobacteriosis infection (one), tuberculosis (one), lymphoma (one), and weight loss (four). Active viral hepatitis was found in all patients. All patients were hepatitis C antibody-positive. Hepatitis C RNA was found in six, delta hepatitis antigen in two, and one was HBs-antigen positive. THE LANCET

The antibacterial activity of topical retinoids: the case of retinaldehyde.

Background: Retinoids such as retinoic acid (RA), retinol (ROL) and retinaldehyde (RAL) are currently used in many formulations and indications ranging form acne to skin aging. Most if not all their pharmacological activities occur through binding to nuclear receptors with subsequent modulation of the activities of several genes. Little attention has been given to the many other potential actions on the surface of the skin. Aim: To analyse the potential anti-infective activities of topical ROL, RAL and RA. Methods: Microbial minimal inhibitory concentrations (MIC) of ROL, RAL and RA were determined by a microdilution method on reference strains including Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus flavus, Propionibacterium acnes, Micrococcus luteus, Enterococcus faecium,Staphylococcus hominis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and 133 clinical strains including methicillin-resistant S. aureus, methicillin-sensitive S. aureus, coagulase-negative Staphylococcus, Streptococcus group B, Enterococcus faecalis, vancomycin-resitant E. faecalis, vancomycin-resistant E. faecium and Pseudomonas/Klebsiella. In two clinical trials in healthy human volunteers, skin bacterial densities were evaluated in samples obtained with the cylinder scrub method: (1) 2 and 5 h after a single application of 0.05% RAL or vehicle on the forearm and (2) in a single-blind randomized study where 0.05% RAL or vehicle were applied daily for 2 weeks on the forehead of 22 volunteers. Paired results from treated (or vehicle) and untreated areas were analysed. Results: Of the three retinoids tested, only RAL showed a significant in vitro antibacterial activity; this activity was found against reference strains of gram-positive bacteria like S. aeureus, Micrococcus spp. or P. acnes. No activity was found against gram-negative bacteria. These results on reference strains were confirmed on 133 clinical isolates. MIC50 and MIC90 values for RAL were 8 and 16 mg/l, respectively, for methicillin-sensitive S. aureus and 4 and 8 mg/l for methicillin-resistant S. aureus. The two in vivo studies showed that areas treated with RAL had a significant decrease in the bacterial counts. In the forehead study, the median decrease was 102 log/cm2 for P. acnes and 101.8 log/cm2 for staphylococci. No resistant bacteria were found after 2 weeks of topical use. Preliminary results suggest that the antibacterial effect of RAL is due, in part, to the aldehyde group in the lateral chain, since non-retinoid pseudo-analogues of the chain, like citral and hexenal, showed a similar antibacterial activity. Conclusion: We have shown that RAL differs from parent natural retinoids such as ROL and RA in demonstrating significant antibacterial activities upon topical use. This activity is likely due to the aldehyde group in the isoprenoic lateral chain, which illustrates the potential bifunctional properties of some retinoids.

Human herpes-virus 8 seropositive patient with skin and graft Kaposi’s sarcoma after lung transplantation

Kaposis sarcoma (KS) has been reported after solid organ transplantation mostly in recipients of renal, liver, heart, and bone allografts. We describe the first case of a patient with lung transplantation who developed KS of the skin, but also of the lung graft. The tumors were localized to places of previous trauma, implying the involvement of a Koebner phenomenon. Moreover, a polymerase chain reaction assay revealed the presence of DNA sequences of herpesvirus 8 (HHV-8) on tissue of the cutaneous KS. Serological tests showed HHV-8 seronegativity of the graft donor and HHV-8 seropositivity of the patient before lung transplantation suggesting that the latter was already infected before the surgery and that immunosuppression resulted in the development of KS. This case report raises the question of the prevalence of HHV-8 in candidates for transplantation and organ donors, and of the value of an antiviral prophylaxis to lower the risk of KS.

Malassezia spp Carriage in Patients with Seborrheic Dermatitis

The role of Malassezia spp in seborrheic dermatitis (SD) is controversial. To compare the cutaneous density and the cultural characteristics of Malassezia in persons with or without SD, quantitative cultures were obtained by stripping the forehead with a tape placed on Leeming and Notman medium. Plates were incubated at 37°C in a plastic bag, and colonies were counted after 14 days. High yeast density was defined as >100 colony forming units (CFU)/tape. Volunteers were divided into four groups depending on their HIV serology [HIV (+) versus HIV (‐) or unknown] and their clinical status (with or without SD). 126/129 cultures were positive (97.7%). Malassezia spp density was low on clinically normal skin in all HIV (‐) persons (40/40) but was high in 8/34 (24%) HIV (+) persons without SD (p<0.001). In SD patients, high densities were found in 10/22 (45%) HIV (+) and in 17/33 (52%) HIV (‐) persons. The strains could be divided into three basic groups on the basis of their cultural characteristics. Colony morphology type A predominated on normal skin (72%), and morphology type C predominated on persons with SD (78%). High yeast density can be present without skin symptoms. The pathogenicity of Malassezia seems more likely to be determined by the subtype present on the skin rather than by its density.

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.

Treatment of Acyclovir-Resistant Herpetic Ulceration with Topical Foscarnet and Antiviral Sensitivity Analysis

Background: Herpes simplex virus (HSV) can produce persistent mucocutaneous disease in patients with the acquired immunodeficiency syndrome (AIDS). In this case report, we evaluate the efficacy, safety and viral resistance after topical foscarnet in severe genital ulceration due to acyclovir-resistant HSV-2. Case Report: A 45-year-old African woman was known for an HIV infection with severe immunosuppression (CD4 <100/mm3). She had received a long-term prophylaxis with acyclovir (400 mg b.i.d.) for a recurrent genital herpes. Few weeks after stopping this prophylaxis, she developed large genital ulcerations progressing despite valacyclovir treatment (1,000 mg t.i.d.). Cultures were positive for HSV-2, resistance to acyclovir was shown by the plaque reduction assay and topical foscarnet was tried. Treatment consisted of a 20-min application of topical foscarnet 2.4% twice a day. Dramatic improvement was observed with rapid antalgia, and cicatrization of the genital ulcerations was observed after 50 days. HSV could not be detected on the mucosal surface. Initially, HSV-2 was resistant to acyclovir but sensitive to foscarnet. After 1 month of topical treatment, HSV-2 became sensitive to acyclovir and was still sensitive to foscarnet. Finally, after 6 weeks of treatment, no virus could be detected by culture. Conclusion: Topical foscarnet (2.4%) is a convenient treatment for chronic genital herpes. Resistance to acyclovir disappears few weeks after stopping this drug and sensitivity to foscarnet persists during the 50 days of treatment.

Antibacterial Activity of Retinaldehyde against Propionibacterium acnes

Background: Retinaldehyde has been shown to exert antibacterial activity in vitro. Aim: This study evaluates the effect of retinaldehyde on Propionibacterium acnes both in vivo and in vitro. Methods: Microbial minimal inhibitory concentrations (MICs) of retinaldehyde and retinoic acid were determined on reference strains of P. acnes. In vivo activity of daily topical application of 0.05% retinaldehyde on the P. acnes density was evaluated after application in a single-blind randomised study. Results: MICs of retinaldehyde were 4 mg/l for P. acnes No. CIP179 and CIP53119 and 8 mg/l for P. acnes No. CIP53117. In contrast, the MICs of retinoic acid were superior to 128 mg/l for these three strains. In vivo, retinaldehyde-treated areas displayed a significant decrease in counts of viable P. acnes as compared with the untreated areas with a median decrease of 102 log P. acnes/cm2 after 2 weeks of daily application. Vehicle alone had no effect. Conclusion: The MIC of retinaldehyde against P. acnes suggests a direct antibacterial activity. Daily topical application of 0.05% retinaldehyde is associated with a clear reduction of the P. acnes density.

Neutrophil Eccrine Hidradenitis in a Patient with AIDS

Neutrophilic eccrine hidradenitis (NEH), first described as a rare, transient, and benign complication of various chemotherapy regimens for acute leukemia, has also been observed in other conditions, including three HIV‐positive patients and even in otherwise healthy individuals (1–3). A similar histological pattern was described after intradermal bleomycin injections into normal human skin (4). We report the first case of NEH in a hemophilic HIV infected patient treated with stavudine, a new reverse transcriptase inhibitor.

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.