Diffuse skin findings secondary to lymph node tularemia in a patient with chronic rheumatoid arthritis on methotrexate.

Tularemia has many atypical presentations which can represent a diagnostic challenge. The history is essential in the investigation of this disease. Bite-induced primary skin lesions should be distinguished from the infrequent immune-mediated secondary skin lesions. Herein, we present an atypical pseudovesicular rash secondary to Francisella tularensis.

Metastatic melanoma: spontaneous occurrence of auto antibodies is a good prognosis factor in a prospective cohort.

BACKGROUND: Melanoma is an immunogenic tumour type frequently associated with spontaneous auto-immune manifestations such as spontaneous regression, vitiligo-like reactions or auto-immune retinopathy, which seem to be associated with better prognosis. OBJECTIVES: The aim of this prospective study was to evaluate the correlation between spontaneous autoimmunity and survival in patients with stage IV melanoma. METHODS: From 2007 to 2008, 103 patients were studied with antithyroid and antinuclear auto antibody assays performed every 6 months. Any detectable occurrence of a spontaneous self antibody (SpSA) at the upper detection limit, at least for one assay, was considered to be a biological marker of autoimmunity. RESULTS: Univariate and multivariate analyses confirmed significantly longer survival in the absence of known primary melanoma (P = 0.044) and in the presence of marker of biologic autoimmunity, independently of previous immunotherapy (P = 0.045). CONCLUSIONS: This prospective and comparative study is, to our knowledge, the first to report the frequency of SpSA in stage IV melanoma. Our results suggest that spontaneous autoimmunity, through a rupture of self-tolerance, is a good prognostic factor in a subgroup of patients with stage IV melanoma.

[Merkel cell carcinoma: a new radiation-induced cancer?]. / Carcinome de Merkel : un nouveau cancer radio-induit ?

BACKGROUND: Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumour, appears primarily on sun-exposed areas in light-skinned elderly subjects. UV exposure and profound immunosuppression (particularly in a setting of solid organ transplantation, haematological malignancies, HIV) constitute the principal risk factors. The aetiopathogenesis of this cancer is not known, although a polyomavirus involved in the oncogenic process was recently discovered. The carcinogenic effect of ionizing radiation, while not clearly established, has been suspected in rare cases involving the onset of MCC in irradiated zones. We report a new case of case of MCC in a patient previously undergoing radiotherapy. CASE REPORT: A 59-year-old-man underwent radiotherapy for a Darier-Ferrand dermatofibrosarcoma on the left shoulder and developed MCC at the same site 38 years later. DISCUSSION: The time between radiotherapy and diagnosis of MCC, its site within the radiation field (radio-dermatitis), the description of similar cases in the literature concerning the onset of MCC in irradiated areas, and the known carcinogenic effects of ionizing radiation all militate strongly in favour of the radiation-induced nature of MCC.

[Intravascular lymphoma revealed by generalized arborescent telangiectasia and repeated venous thrombosis]. / Thromboses veineuses récidivantes et télangiectasies arborescentes généralisées révélatrices d'un lymphome intravasculaire.

BACKGROUND: Intravascular lymphoma is a rare form of non-Hodgkin's lymphoma characterized by proliferation of lymphoid cells within the lumen of small veins, small arteries and capillaries. CASE REPORT: A 79-year-old man presented with repeated superficial venous thrombosis of the lower limbs associated with diffuse telangiectasia of the trunk, upper arms and thighs but with normal epidermis. Screening for thrombophilia and neoplasm were negative. The patient subsequently developed abdominal pain, lower-limb oedema, deterioration in performance status and rapidly increasing telangiectasia with the appearance of generalized oedematous cutaneous induration. Increased LDH and anaemia were observed without other blood count anomalies. Intravascular lymphoma was diagnosed on a skin biopsy with telangiectasia and oedema. After eight courses of treatment with rituximab-CHOP the outcome was good. DISCUSSION: A few telangiectasias associated with nodules or infiltrated plaques are often a clinical manifestation of intravascular lymphoma. The dermatological presentation described here is interesting for two reasons: on the one hand, telangiectasias were initially isolated in normal epidermis without any infiltration for more than one year and, on the other hand, the skin infiltration seen subsequently was very extensive and marked. Moreover, although microthrombi are frequent in small and medium-sized blood vessels, thrombosis of large vessels is rarely described in intravascular lymphoma.

[Topical haemotherapy as treatment for necrotic angiodermatitis: a pilot study]. / Autohémothérapie locale dans l'angiodermite nécrotique: étude pilote.

INTRODUCTION: Necrotic angiodermatitis is a variety of leg ulcer, characterized by very painful and rapidly spreading lesions. Healing takes time, a mean of 4 to 11 months. Current treatment is difficult and rarely satisfactory. Only early skin grafts lead to rapid sedation of pain and stop the lesion from extending. However, this technique, performed during a progressive phase, enhances the risk of losing a certain number of grafts. We wanted to confirm the efficacy of local auto-haemo-therapy proposed in 2 non-controlled studies. PATIENTS AND METHODS: Eleven patients with necrotic angiodermatitis were included in our non-controlled prospective study. The topical hemotherapy was applied three times a week for one month, with initial hospitalization for 15 days. The criteria of assessment were: evolution of pain, surface of the ulcer, colorimetric scale and the date of disappearance of the purple halo. RESULTS: Ten patients were relieved by the treatment, with progressive withdrawal of the analgesics. The progression of the lesion had stopped and the purple halo had disappeared in general by D6 (range: 2 to 21 days). The percentage of granulation tissue with regard to the surface of the ulcer was of 45.4 p. 100 on D0, 80 p. 100 on D14 and 85 p. 100 on D28. CONCLUSION: Topical hemotherapy applied during the initial phase of treatment would reduce the pain and prepare the lesion for a secondary skin graft.

[Cardiac troponin I and CK-MB mass after cardiac surgery with cardiopulmonary bypass]. / Troponine Ic et CK-MB masse en chirurgie cardiaque sous circulation extracorporelle.

Cardiac troponin I (cTnI) assay is used in the diagnosis of myocardial infarction after cardiac surgery. Variations in the cut-off value have been reported even with the same assay method. The aim of this work is to investigate the release profile of cTnI and CK-MB mass after cardiac surgery and to determine the cut-off value of cTnI and CK-MB mass allowing the diagnosis of perioperative myocardial infarction. In patients without postoperative cardiac complication, the cTnI peak was observed 24 hours after surgery both in coronary artery bypass grafting and in valve replacement. Moreover, the amount of cTnI released within the three hours after surgery is 2.5 fold higher in valve replacement than in coronary artery bypass grafting. The CK-MB peak was observed 3 hours after surgery in the two surgical procedures. In these patients, cTnI and CK-MB concentrations increased with the cross clamp time duration. In patients with postoperative myocardial infarction, the cTnI and CK-MB peaks were observed 24 hours after surgery. Diagnosis of perioperative myocardial infarction can be performed with a sensitivity of 100% at 24 hours with cut-off values of 32 and 7 microg/L for CK-MB and cTnI, respectively, both with Stratus (Dade Behring) and Immulite (DPC) analysers.

[Treatment of solar urticaria by intravenous immunoglobulins and PUVA therapy]. / Urticaire solaire traitée par l'association immunoglobulines polyvalentes et PUVAthérapie.

BACKGROUND: Solar urticaria is a rare form of urticaria occurring a few minutes after solar exposure. It is particularly incapaciting because it limits outdoor activities. Antihistamine and phototherapy are sometimes disappointing. CASE REPORT: A 32 Year-old woman had been suffering from severe solar urticaria since November 2000, which was confirmed by photobiological data. High-dose antihistamine treatment (fexofenadine 180 mg twice a day) was inefficient. Despite a first UVA desensitization, PUVAtherapy produced only a partial improvement and short lasting for protection, with an important handicap in daily life. In March 2002, among the others treatments, we chose intravenous immunoglobulins: 0.5 g/kg the first day then 1 g/kg the second and the third days. The minimal urticaria dose was raised from 1 J/cm2 in UVA before perfusion up to 15.6 J/cm2 48 hours later and in UVB from 100 mJ/cm2 up to 2,200 mJ/cm2. Clinically the improvement was significant but partial in daily activities. It was possible to reintroduce PUVAtherapy without UVA-desensitization and, for the first time, to obtain complete remission for more than 2 Months with an association of intravenous immunoglobulins, PUVAtherapy and antihistamine treatment. In July 2002, treatment was successfully repeated. DISCUSSION: First intention treatments (antihistamine and PUVAtherapy) are sometimes inefficient. Others treatments (plasmapheresis, ciclosporin, doxepin, cimetidine) are restrictive, not always efficient and can induce severe side-effects. We report the second case of solar urticaria improved by intravenous immunoglobulins. In spite of the cost, intravenous immunoglobulins seem to be an interesting treatment, at least by avoiding UVA-desensitization in severe cases of solar urticaria.

The BMP signaling pathway is required together with the FGF pathway for notochord induction in the ascidian embryo.

The 40 notochord cells of the ascidian tadpole invariably arise from two different lineages: the primary (A-line) and the secondary (B-line) lineages. It has been shown that the primary notochord cells are induced by presumptive endoderm blastomeres between the 24-cell and the 64-cell stage. Signaling through the fibroblast growth factor (FGF) pathway is required for this induction. We have investigated the role of the bone morphogenetic protein (BMP) pathway in ascidian notochord formation. HrBMPb (the ascidian BMP2/4 homologue) is expressed in the anterior endoderm at the 44-cell stage before the completion of notochord induction. The BMP antagonist Hrchordin is expressed in a complementary manner in all surrounding blastomeres and appears to be a positive target of the BMP pathway. Unexpectedly, chordin overexpression reduced formation of both primary and secondary notochord. Conversely, primary notochord precursors isolated prior to induction formed notochord in presence of BMP-4 protein. While bFGF protein had a similar activity, notochord precursors showed a different time window of competence to respond to BMP-4 and bFGF. Our data are consistent with bFGF acting from the 24-cell stage, while BMP-4 acts during the 44-cell stage. However, active FGF signaling was also required for induction by BMP-4. In the secondary lineage, notochord specification also required two inducing signals: an FGF signal from anterior and posterior endoderm from the 24-cell stage and a BMP signal from anterior endoderm during the 44-cell stage.

The BMP/CHORDIN antagonism controls sensory pigment cell specification and differentiation in the ascidian embryo.

We have investigated the role of the bone morphogenetic protein (BMP) pathway during neural tissue formation in the ascidian embryo. The orthologue of the BMP antagonist, chordin, was isolated from the ascidian Halocynthia roretzi. While both the expression pattern and the phenotype observed by overexpressing chordin or BMPb (the dpp-subclass BMP) do not suggest a role for these factors in neural induction, BMP/CHORDIN antagonism was found to affect neural patterning. Overexpression of BMPb induced ectopic sensory pigment cells in the brain lineages that do not normally form pigment cells and suppressed pressure organ formation within the brain. Reciprocally, overexpressing chordin suppressed pigment cell formation and induced ectopic pressure organ. We show that pigment cell formation occurs in three steps. (1) During cleavage stages ectodermal cells are neuralized by a vegetal signal that can be substituted by bFGF. (2) At the early gastrula stage, BMPb secreted from the lateral nerve cord blastomeres induces those neuralized blastomeres in close proximity to adopt a pigment cell fate. (3) At the tailbud stage, among these pigment cell precursors, BMPb induces the differentiation of specifically the anterior type of pigment cell, the otolith; while posteriorly, CHORDIN suppresses BMP activity and allows ocellus differentiation.

Animal and vegetal pole cells of early Xenopus embryos respond differently to maternal dorsal determinants: implications for the patterning of the organiser.

The maternal dorsal determinants required for the specification of the dorsal territories of Xenopus early gastrulae are located at the vegetal pole of unfertilised eggs and are moved towards the prospective dorsal region of the fertilised egg during cortical rotation. While the molecular identity of the determinants is unknown, there are dorsal factors in the vegetal cortical cytoplasm (VCC). Here, we show that the VCC factors, when injected into animal cells activate the zygotic genes Siamois and Xnr3, suggesting that they act along the Wnt/beta-catenin pathway. In addition, Siamois and Xnr3 are activated at the vegetal pole of UV-irradiated embryos, indicating that these two genes are targets of the VCC factors in all embryonic cells. However, the consequences of their activation in cells that occupy different positions along the animal-vegetal axis differ. Dorsal vegetal cells of normal embryos or VCC-treated injected animal cells are able to dorsalise ventral mesoderm in conjugate experiments but UV-treated vegetal caps do not have this property. This difference is unlikely to reflect different levels of activation of FGF or activin-like signal transduction pathways but may reflect the activation of different targets of Siamois. Chordin, a marker of the head and axial mesoderm, is activated by the VCC/Siamois pathway in animal cells but not in vegetal cells whereas cerberus, a marker of the anterior mesendoderm which lacks dorsalising activity, can only be activated by the VCC/Siamois pathway in vegetal cells. We propose that the regionalisation of the organiser during gastrulation proceeds from the differential interpretation along the animal-vegetal axis of the activation of the VCC/beta-catenin/Siamois pathway.

A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone.

We have studied the role of the activin immediate-early response gene Mix.1 in mesoderm and endoderm formation. In early gastrulae, Mix.1 is expressed throughout the vegetal hemisphere, including marginal-zone cells expressing the trunk mesodermal marker Xbra. During gastrulation, the expression domains of Xbra and Mix.1 become progressively exclusive as a result of the establishment of a negative regulatory loop between these two genes. This mutual repression is important for the specification of the embryonic body plan as ectopic expression of Mix.1 in the Xbra domain suppresses mesoderm differentiation. The same effect was obtained by overexpressing VP16Mix.1, a fusion protein comprising the strong activator domain of viral VP16 and the homeodomain of Mix.1, suggesting that Mix.1 acts as a transcriptional activator. Mix.1 also has a role in endoderm formation. It cooperates with the dorsal vegetal homeobox gene Siamois to activate the endodermal markers edd, Xlhbox8 and cerberus in animal caps. Conversely, vegetal overexpression of enRMix.1, an antimorphic Mix.1 mutant, leads to a loss of endoderm differentiation. Finally, by targeting enRMix.1 expression to the anterior endoderm, we could test the role of this tissue during embryogenesis and show that it is required for head formation.