L. Raffray

Septic shock sera containing circulating histones induce dendritic cell-regulated necrosis in fatal septic shock patients.

Objectives:Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis. Design:Prospective, controlled experimental study. Setting:Research laboratory at an academic medical center. Subjects:The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers. Interventions:Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining. Measurements and Main Results:We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p < 0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell–regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell–regulated necrosis. Conclusions:The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease.

Characteristics and Management of IgA Vasculitis (Henoch-Schonlein) in Adults Data From 260 Patients Included in a French Multicenter Retrospective Survey

Data on adult IgA vasculitis (Henoch‐Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Characteristics and management of IgA vasculitis (Henoch-Schönlein purpura) in adults: Data from the 260 patients included in the IGAVAS survey

Data on adult IgA vasculitis (Henoch‐Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Hepatic Visceral Larva Migrans Presenting as a Pseudotumor

h c d l f n i A woman was referred for the assessment of a focal hepatic lesion of fortuitous discovery. The patient’s edical history was remarkable for adenocarcinoma of the reast that had been in remission for 10 years. Routine laboraory results including liver test function and tumor markers ere within normal limits. Imaging study revealed a unique odular lesion of 26 mm in hepatic segment IV, hyperechoic in bdominal ultrasonography, and low density in computed toography (Figure A, arrow). Magnetic resonance imaging showed a nodule that exhibited low intensity in T2 (Figure B, arrow) and high intensity in T1 and presented slightly heterogeneous contrast enhancement after gadolinium injection. Imaging characteristics ruled out focal steatosis, angioma, or focal nodular hyperplasia. In the context of malignancy history, ultrasound-guided liver biopsy of the lesion was conducted. Histologic analysis showed an encapsulated abscess (Figure C). At higher magnification (Figure D), it was made of a mixture of necrotic hepatocytes and large amounts of altered eosinophils, and many Charcot–Leyden crystals, appearing as refringent yellowish spindle-cell structures, were irregularly scattered among these cells. No parasitic structures were visible. Tumoral process was absent. Serologic antibody testing for various helminthic infections was negative except for Toxocara canis, with a titer of 34 U in enzyme-linked immunosorbent assay (normal range, 9 U), and confirmatory Western blot test showed 5 positive bands (normal, 2). This resulted in the conclusive diagnosis of visceral toxocariasis. The patient was managed with albendazole 400 mg 3 times a day associated with ivermectin 12 mg per week for a total of 3 weeks. Magnetic resonance imaging control 6 months after treatment was normal, consistent with favorable outcome. Toxocara canis is the main cause of visceral larva migrans in humans. It may affect multiple visceral organs, and the liver is the most involved site, usually mimicking tumoral processes.1 Lesions are usually described as oval, ill-defined nodules, either unique or more frequently multiple.2,3 Noninvasive approach as been advocated for contributing to diagnostic issue by ombining imaging and serologic testing. Visceral larva migrans iagnosis is to be ascertained when managing investigations for iver nodules caused by eosinophilic infiltrate to disclose them rom metastatic deposits. Treatment of symptomatic forms is ot well codified, and albendazole alone or in combination with vermectin has been reported to be effective.

Hépatite granulomateuse révélant une infection disséminée à Mycobacterium bovis après BCG-thérapie intravésicale Hépatite granulomateuse révélant une infection disséminée à Mycobacterium bovis après BCG-thérapie intravésicale.

INTRODUCTION Intravesical therapy with bacillus Calmette-Guérin (BCG) has proved to be effective in the treatment of superficial bladder tumors. Side-effects include local infections and rarely disseminated BCG infection with multiple end organ complications such as granulomatous hepatitis, pneumonitis, aortitis and bone marrow involvement. CASE REPORT We report an 83-year-old man who presented with chronic granulomatous hepatitis. This was related to intravesical BCG therapy received two years earlier for superficial bladder cancer. Aortitis, splenic infarction and hematopoietic involvement were also diagnosed. Outcome was favorable following adapted antibiotic course. CONCLUSION This case report highlights the possibility of widespread BCG infection following intravesical treatment, and the need for vigilance in patients with a history of such a therapy even several years later.

Treatment of Eosinophilic Granulomatosis with Polyangiitis: A Review

Eosinophilic granulomatosis with polyangiitis (formerly Churg–Strauss syndrome) is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis. Nevertheless, eosinophilic granulomatosis with polyangiitis stands apart because it has features of vasculitis and eosinophilic disorders that require targeted therapies somewhat different from those used for other anti-neutrophil cytoplasm antibody-associated vasculitides. Considerable advances have been made in understanding the underlying pathophysiology of eosinophilic granulomatosis with polyangiitis that have highlighted the key role of eosinophils and opened new therapeutic opportunities. Its conventional treatment relies mainly on agents that decrease inflammation: corticosteroids and immunosuppressant adjunction for severe manifestations. New therapeutic approaches are needed for refractory disease, relapses and issues associated with corticosteroid dependence, especially for asthma manifestations. Drugs under evaluation mostly target eosinophils and B cells. Results of low-evidence-based trials suggested possible efficacies of biologicals: B-cell-blocking rituximab and anti-immunoglobulin E omalizumab. Recently, the first large-scale randomised controlled trial on eosinophilic granulomatosis with polyangiitis proved the efficacy of anti-interleukin-5 mepolizumab. That finding opens a new era in eosinophilic granulomatosis with polyangiitis management, with mepolizumab approval but also in future drug evaluations and trial designs for eosinophilic granulomatosis with polyangiitis. Additional studies are needed to determine which patients would benefit most from targeted therapies and achieve personalised treatment for patients with eosinophilic granulomatosis with polyangiitis. Herein, we review eosinophilic granulomatosis with polyangiitis characteristics and provide an overview of established and novel pharmacological agents.