Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Whole-body MRI with diffusion-weighted sequences compared with 18 FDG PET-CT, CT and superficial lymph node ultrasonography in the staging of advanced cutaneous melanoma: a prospective study.

OBJECTIVES: The aim of our study was to compare the diagnostic performances of non-radiating whole-body magnetic resonance imaging (wbMRI), either volumetric, with Volumetric interpolated breath-hold examination (VIBE) or metabolic, with diffusion-weighted sequences (wbMRI), with classical irradiating techniques such as PET-CT, CT and with lymph node ultrasonography (US) for the staging of advanced melanoma. PATIENTS AND METHODS: Thirty-seven melanoma AJCC stage IV patients were prospectively included. All images were independently interpreted without prior knowledge of the results of studies performed with concurrent techniques, and all imaging techniques were scheduled within a mean interval of 7 days. The overall and site-specific diagnosis performances of each imaging modality were studied, as well as the interest of combined MRI VIBE and diffusion sequences. RESULTS: The number of visceral or lymph node metastases spotted was, respectively, 218, with 125 metastases for wbMRI, 191/103 for PET-CT, 209/115 for CT and 33/13 for lymph node US. No statistically significant difference (P < 0.05) of overall diagnostic performances between wbMRI (Se 84%, Sp 87.1%, PPV 89.8%, NPV 80.2%) and PET-CT (Se 79.8%, Sp 93.1%, PPV 93.2%, NPV 79.4%) was observed. No statistically significant difference was found between wbMRI and PET-CT with two channels for CT with respect to different metastatic sites. Compared with the CT, wbMRI had significantly better overall specificity (P = 0.0011) and PPV (P = 0.02). For lung exploration, sensitivity of wbMRI (51.6%) was inferior to CT (71.4%). To detect superficial metastatic lymph nodes, wbMRI and US both showed high diagnostic accuracy with no statistically significant difference. Intra-observer agreement was almost perfect for all imaging modalities considering the overall staging. Inter-observer agreement for wbMRI and diffusion alone was almost perfect except for bone and lymphatic sites. Overall diagnostic performance of diffusion alone was significantly inferior to those of combined VIBE and diffusion sequences. CONCLUSIONS: Whole-body MRI, using diffusion weighted sequences, was a reliable non-radiating imaging for staging of melanoma and offers the same diagnostic performances than combined CT, PET-CT and lymph node US.

The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses.

Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinoma and glioblastoma multiforme cell lines were grafted on the CAM of embryonated chicken eggs. All cell lines tested formed 5-10 mm size tumors, which recapitulated hallmarks of corresponding human specimens. Furthermore, melanoma tumors were injected with adenoviral vector-carrying gene encoding the fusion protein of parainfluenza virus type 5. This led to the induction of cell fusion and syncytia formation in the infected cells. At 6 days post-injection, histological and immunohistochemical analyses of tumor sections confirmed adenovirus replication and syncytia formation. These results demonstrate that the CAM model allows rapid assessment of oncolytic viruses in three-dimensional tumors. Hence, this model constitutes an easy and affordable system for preclinical characterization of viral oncolytic agents that may precede the mandatory process of animal testing. Application of this model will help reducing the use of human xenografts in mice for preclinical evaluation of oncolytic viruses and other anticancer agents.

Engineering of a parainfluenza virus type 5 fusion protein (PIV-5 F): development of an autonomous and hyperfusogenic protein by a combinational mutagenesis approach.

The entry of enveloped viruses into host cells is accomplished by fusion of the viral envelope with the target cell membrane. For the paramyxovirus parainfluenza virus type 5 (PIV-5), this fusion involves an attachment protein (HN) and a class I viral fusion protein (F). We investigated the effect of 20 different combinations of 12 amino-acid substitutions within functional domains of the PIV-5 F glycoprotein, by performing cell surface expression measurements, quantitative fusion and syncytia assays. We found that combinations of mutations conferring an autonomous phenotype with mutations leading to an increased fusion activity were compatible and generated functional PIV-5 F proteins. The addition of mutations in the heptad-repeat domains led to both autonomous and hyperfusogenic phenotypes, despite the low cell surface expression of the corresponding mutants. Such engineering approach may prove useful not only for deciphering the fundamental mechanism behind viral-mediated membrane fusion but also in the development of potential therapeutic applications.

Prevalence of Staphylococcus aureus toxins and nasal carriage in furuncles and impetigo.

BACKGROUND: The precise role of Staphylococcus aureus toxins and nasal carriage in common skin infections remains unclear. OBJECTIVES: To seek correlations between toxin expression, S. aureus nasal carriage and clinical manifestations in patients with community-acquired furuncles and impetigo. METHODS: From November 2004 to August 2005, we studied clinical data and bacteriological samples prospectively collected from 121 patients presenting with furuncles or impetigo. RESULTS: Sixty-four patients (31 with furuncles and 33 with impetigo) had S. aureus-positive skin culture. Panton-Valentine leukocidin (PVL) genes were present in 13 of 31 (42%) isolates from furuncles and were associated with epidemic furunculosis. Exfoliative toxin genes were present in 10 of 10 (100%) and 12 of 21 (57%) bullous and nonbullous impetigo isolates, respectively. Nasal carriage of S. aureus was found in 58% of patients overall. It was strongly associated with chronic furunculosis but not with simple furuncles (88% vs. 29%, P < 0.007). Skin and nose isolates from a given patient always had identical characteristics. Methicillin-resistant S. aureus accounted for four of 64 (6%) positive skin cultures. CONCLUSIONS: PVL is not involved in all types of furuncles but is associated with epidemic furunculosis. Both bullous and nonbullous forms of impetigo are associated with exfoliative toxins. Staphylococcus aureus nasal carriage is associated with the chronicity of furuncles.

Does erysipelas-like rash after hip replacement exist?

BACKGROUND: Orthopaedic implants are known to rarely induce or exacerbate dermatitis in metal-allergic patients. In the late 1990s, hypersensitivity to prosthetic material has been suspected to induce recurrent aseptic localized cellulitis. Patients presented with recurrent eruption of the skin overlying the implant, associated with fever. An aseptic origin of this new syndrome was hypothesized as no evidence of microbial involvement could be found and because antibiotic treatment was apparently inefficient. OBSERVATIONS: We observed 4 similar cases. All patients recovered after suppression of factors predisposing to erysipelas (gluteal portal of entry, anti-inflammatory drugs) and appropriate antibiotic therapy. DISCUSSION: Our conviction is that these manifestations are authentic infectious cellulitis. Delayed thigh erysipelas after hip surgery is a distinctive form of cellulitis, characterized by its unusual topography, its rapid outcome and the possibility to be recurrent.

Emergence of two populations of methicillin-resistant Staphylococcus aureus with distinct epidemiological, clinical and biological features, isolated from patients with community-acquired skin infections.

BACKGROUND: Community-acquired skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) are an emerging clinical and epidemiological problem. OBJECTIVES: To characterize community-acquired skin infections caused by S. aureus, and especially MRSA. METHODS: From November 1999 to December 2003, we conducted in a French hospital a prospective epidemiological, clinical and bacteriological study of skin infections acquired in the community, applying strict criteria for true community-acquired MRSA (CA-MRSA) and health-care-associated MRSA (HCA-MRSA). RESULTS: One hundred and ninety-seven patients had 207 skin infections (154 primary and 53 secondary infections). Twenty-two (11%) patients had skin infections caused by MRSA. The incidence of MRSA skin infections acquired in the community rose from 4% in 2000 to 17% in 2003, but the increase was not statistically significant. Six patients (3%) were infected by CA-MRSA and 15 (8%) by HCA-MRSA; one patient was lost to follow-up and could not be classified. CA-MRSA and HCA-MRSA had different epidemiological, clinical and biological characteristics. CA-MRSA infections were more severe than HCA-MRSA infections: all the CA-MRSA infections (six of six, 100%) required surgical treatment, compared with only two (15%) of 13 with HCA-MRSA infection (P < 0.001). CA-MRSA all belonged to the same clonal strain, harbouring an agr type 3 allele and the Panton-Valentine leucocidin genes (not detected in HCA-MRSA) and possessing a specific antibiotype. CONCLUSIONS: Two populations of MRSA causing skin infections are emerging in the French community, with distinct epidemiological, clinical and biological characteristics.