Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has been associated with a marked decrease in the prevalence of opportunistic infections in HIV-infected patients. However, chronic mucocutaneous herpes simplex virus (HSV) infection remains a difficult clinical challenge. OBJECTIVE: The aim of the study was to optimize the diagnosis and follow-up of chronic HSV-2 infection in HIV-infected patients and to correlate clinical data with CD4 cell count, in vitro HSV virological resistance and histology. METHODS: A retrospective case series was collected from a specialist out-patient clinic providing consultations to patients with infectious skin diseases. Clinical, biological, virological and histological data were analysed. RESULTS: Seven HIV-infected patients with genital and perianal herpes simplex infection were followed over 10 years. Ulcerative and pseudo-tumoral forms were observed. Lesions occurred at various stages of immune suppression (CD4 counts from 1 to 449 cells/µL). Clinical resistance to conventional anti-herpetic drugs was correlated with the in vitro resistance of HSV in 70% of cases. CONCLUSIONS: Chronic mucocutaneous HSV infection in AIDS patients remains a rare but regularly observed infection in very immunosuppressed patients or those with unstable immunity during HAART. Virological results obtained from mucocutaneous samples were in most cases found to be correlated with clinical evolution and should therefore be used in making decisions on treatment. Despite efficient antiviral therapy, mucocutaneous healing is slow in the majority of cases.

[Cutaneous complications of anti-hypertensive drugs]. / Complications cutanées des traitements anti-hypertenseurs.

Anti-hypertensive drugs are prescribed frequently and can cause cutaneous adverse drug reactions. The extent of this side effect accounts for about 10-60% of the total adverse drug reactions due to antihypertensive drugs. This review analyses anti-hypertensive drugs by class and examines various cutaneous pathologies that could be related to these treatments. We also call attention to the serious and potentially lethal cutaneous complications linked to these drugs.

[Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients]. / 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.

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-resistant 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. MIC(50) and MIC(90) 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 10(2) log/cm(2) for P. acnes and 10(1.8) log/cm(2) 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.

An annular plaque due to Mycobacterium haemophilum infection in a patient with AIDS.

Infections with mycobacteria are of importance in the differential diagnosis of skin lesions in immunocompromised patients. We report the case of a human immunodeficency virus (HIV)-infected patient who presented with an annular plaque as cutaneous manifestation of Mycobacterium haemophilum. Improvement of the immunologic status is important for successful treatment. Complete resolution was only observed when the antimycobacterial therapy was combined with antiretroviral therapy.

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.

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 degrees 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.

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 10(2) log P. acnes/cm(2) 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.

Pseudoporphyria induced by nabumetone.

Nabumetone is a nonsteroidal anti-inflammatory drug, which has only rarely been associated with photosensitivity. We report a case of bullous lesions arising over photoexposed areas in a patient treated with nabumetone.

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

Kaposi's 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.

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.

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.