H. Adamski

Merkel Cell Polyomavirus Small T Antigen mRNA Level Is Increased following In Vivo UV-Radiation

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer involving Merkel cells. Recently, a new human polyomavirus was implicated in MCC, being present in 80% of the samples analyzed. In virus-positive MCC, the Merkel cell polyomavirus (MCPyV) is clonally integrated into the patients DNA, and carries mutations in its large T antigen, leading to a truncated protein. In non-symptomatic tissue MCPyV can reside at very low levels. MCC is also associated with older age, immunosuppression and sun exposure. However, the link with solar exposure remains unknown, as the precise mechanism and steps involved between time of infection by MCPyV and the development of MCC. We thus investigated the potential impact of solar simulated radiation (SSR) on MCPyV transcriptional activity. We screened skin samples of 20 healthy patients enrolled in a photodermatological protocol based on in vivo-administered 2 and 4 J/cm2 SSR. Two patients were infected with two new variants of MCPyV, present in their episomal form and RT-QPCR analyses on SSR-irradiated skin samples showed a specific and unique dose-dependent increase of MCPyV small t antigen transcript. A luciferase based in vitro assay confirmed that small t promoter is indeed UV-inducible. These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure.

Omalizumab in patients with severe and refractory solar urticaria: A phase II multicentric study.

1 4 J/cm (UVA) 5 J/cm 1 J/cm 2 3 J/cm (UVA) 7 J/cm 3 J/cm 3 0.3 J/cm (UVA) 0.5 J/cm 0.2 J/cm 10 mJ/cm (UVB) 10 mJ/cm 10 mJ/cm 4 2 J/cm (UVA) 2 J/cm 2 J/cm 250 mJ/cm ( polyC) \250 mJ/cm \250 mJ/cm 5 0.072 J/cm (UVA) 0.144 J/cm 0.017 J/cm 14 mJ/cm (UVB) 417 mJ/cm 1.8 mJ/cm 6 0.5 J/cm (UVA) 0.5 J/cm ND 61 mJ/cm ( polyC) 107 mJ/cm 7 4 J/cm (UVA) [40 J/cm 0.5 J/cm 8 1 J/cm (UVA) 1 J/cm \1 J/cm 60 mJ/cm (UVB) 60 mJ/cm 1 mJ/cm 9 1 J/cm (UVA) 3 J/cm 1.5 J/cm 10 0.6 J/cm (UVA) [6 J/cm 5 J/cm 80 mJ/cm (UVB) [240 mJ/cm 40 mJ/cm

Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8−2.10−7; P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.

ERK-regulated differential expression of the Mitf 6a/b splicing isoforms in melanoma.

The master regulator of the melanocyte lineage Mitf is intimately involved in development as well as melanoma, controlling cell survival, differentiation, proliferation and metastasis/migration. Consistent with its central role, Mitf expression and Mitf post‐translational modifications are tightly regulated. An additional potential level of regulation is afforded by differential splicing of Mitf exon‐6 leading to the generation of two isoforms that differ by the presence of six amino‐acids in the Mitf (+) isoform and which have differential effects on cell cycle progression. However, whether the ratio of the two isoforms is regulated and whether their expression correlates with melanoma progression is not known. Here, we show that the differential expression of the Mitf 6a/b isoforms is dependent on the MAPKinase signalling, being linked to the activation of MEK1‐ERK2, but not to N‐RAS/B‐RAF mutation status. In addition, quantification of Mitf 6a/b splicing forms in 86 melanoma samples revealed substantially increased levels of the Mitf (−) form in a subset of metastatic melanomas. The results suggest that differential expression of the Mitf 6a/b isoforms may represent an additional mechanism for regulating Mitf function and melanoma biology.

Pyoderma gangrenosum treated with high-dose intravenous immunoglobulins: Two cases and review of the literature.

Pyoderma gangrenosum (PG) is a neutrophilic skin disease commonly treated with immunosuppressants. High-dose intravenous immunoglobulins are used to treat a range of inflammatory diseases, but we found only five reports of the use of high-dose intravenous immunoglobulins in the treatment of PG. We report on two patients with PG for whom immunosuppressants could not be prescribed and who were treated with high-dose intravenous immunoglobulins.Case 1 was a 58-year-old man who presented with a 6-year history of PG. He was initially treated with prednisone. The 20 mg/day dosage of prednisone could not be reduced and treatment had to be discontinued after 1 year because of serious adverse effects. Minocycline treatment led to improvement but had to be discontinued after 6 years because of facial skin hyperpigmentation. Case 2 was a 66-year-old man who presented with a 3-year history of PG. Different therapeutic procedures for PG (prednisone, topical tacrolimus or betamethasone) had failed. High-dose intravenous immunoglobulins were administered monthly at a dose of 2 g/kg for 6 months. The treatment induced stabilisation of the disease and made it possible to reduce corticosteroid use in both patients.These cases show that high-dose intravenous immunoglobulins represent a therapeutic alternative for PG, but the efficacy of this treatment should be confirmed in further studies.

Physicians involved in the care of patients with high risk of skin cancer should be trained regarding sun protection measures: evidence from a cross sectional study

Background  Knowledge, regarding sun protection, is essential to change behaviour and to reduce sun exposure of patients at risk for skin cancer. Patient education regarding appropriate or sun protection measures, is a priority to reduce skin cancer incidence.

Syndrome d’hypersensibilité médicamenteuse (DRESS) au ranélate de strontium

INTRODUCTION Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe form of adverse drug reaction. Strontium ranelate has recently been authorised for postmenopausal osteoporosis. We report a case of strontium ranelate-induced DRESS complicated by linear Ig A dermatosis due to vancomycin. CASE REPORT A 77-year-old woman with osteoporosis had been treated by strontium ranelate for 4 weeks when she developed a febrile generalized skin rash. Blood tests showed eosinophilia (12.74 × 10(9)/L) and liver damage. A diagnosis of DRESS was made, leading to discontinuation of strontium ranelate and prescription of systemic corticosteroids. Two days later, methicillin-resistant Staphylococcus aureus bacteraemia occurred and treatment with vancomycin was started. The liver dysfunction resolved. After two weeks of antibiotherapy, bullous lesions were noted on the thighs. Skin biopsy results suggested a diagnosis of linear IgA bullous dermatosis. Vancomycin was stopped. Two weeks later, the eruption resolved. The eosinophil count gradually returned to normal after four months of corticosteroid therapy. DISCUSSION More than 15 cases of DRESS syndrome have been reported in Europe, including 2 deaths related to ranelate strontium, prompting European health authorities to publish a warning concerning the risk of strontium ranelate-induced DRESS. A particular feature of our patient was complication with linear IgA bullous dermatosis caused by vancomycin. In conclusion, it is essential to be aware of the risk of severe cutaneous reaction to strontium ranelate, a new drug used to treat osteoporosis.

Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma

Mutations of BRAF, NRAS and c‐KIT oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features. BRAF‐, MEK‐ and KIT‐inhibitors led to improvement in overall survival of patients harbouring mutated metastatic melanoma.

Positive photobiological investigation in reticular erythematous mucinosis syndrome

Background: Reticular erythematous mucinosis (REM) syndrome is a rare disorder. Its clinical course is cyclic with remissions and exacerbations. In this disease, photosensitivity has previously been noticed but rarely demonstrated. We report three new cases with positive photobiological investigation.

Primary cutaneous cribriform carcinoma : a rare apocrine tumour

Background:  Primary cutaneous cribriform carcinoma (PCCC) is a rare apocrine tumour occurring in middle‐aged people. This neoplasm is often located on the limbs. The histopathological diagnosis is difficult, mainly because this tumour is exceptional. We, in this study, report a patient with PCCC.