Vascularites des vaisseaux moyens d'origine virale VIH (à propos de deux cas)

Les deux observations présentées lors de ce travail de thèse ont permis de faire une mise au point sur les vascularites survenant au cours d une infection virale VIH L analyse des 64 cas de vascularite publiés depuis une quinzaine d années ont permis un classement de celles-ci. Les vascularites nécrosantes (de critères histologiques d une PAN), classées parmi les vascularites non liées à une infection opportuniste ont comme principale manifestation clinique une neuropathie périphérique, qui touche surtout les petits vaisseaux. L atteinte des moyens vaisseaux, moins fréquente peut se manifester par une gangrène (notamment chez le patient toxicomane. Les atteintes plus diffuses, rénales et digestives sont plus rares. Les vascularites non nécrosantes et non liées à une infection opportuniste, sont responsables d une atteinte clinique polymorphe, tout aussi sévère et qui semble intéresser les vaisseaux de petits calibres. Les vascularites liées à une infection opportuniste représente au moins 16,5% des cas publiés. Enfin, les angéites primitives du système nerveux central (AP SNC) et les lésions angiocentriques immunoprolifératives (LAI) se distinguent par leur présentation clinique et histologique particulière. Le diagnostic des deux patients présentés est une vascularite type panartérite noueuse d origine virale VIH. Les artères rénales, digestives et testiculaires sont touchées. L atteinte coronarienne et artérielle pulmonaire d un des deux patients est étonnante. A notre connaissance, ces deux observations n ont jamais été décrites.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Inflammatory optic neuropathy in granulomatosis with polyangiitis can mimick isolated idiopathic optic neuritis

International audienceOBJECTIVE:We describe a clinico-radiological presentation of inflammatory optic neuropathy that mimicked optic neuritis.METHODS:Retrospective single-center case series and literature review of optic neuropathy without orbital pseudotumor.RESULTS:Five local patients fulfilled the inclusion criteria. Clinical presentation revealed rapidly progressive severe unilateral visual loss, retrobulbar pain (n = 4), and paralytic strabismus (simultaneous = 2, protracted = 2) without proptosis. Optic nerve abnormality was not appreciated on initial scan review. Patients did not have any general activity of the granulomatosis with polyangiitis. Upon follow-up magnetic resonance imaging and initial imaging review, all patients revealed orbital apex anomalies. Visual acuity improved in three patients who received high-dose intravenous glucocorticosteroids immediately. Relapse was frequent and visual outcome was poor (final vision > 20/40 in two patients only). Literature review identified 16 well-documented cases of granulomatosis with polyangiitis-related isolated optic neuropathies. Magnetic resonance imaging revealed no abnormality (n = 6), optic nerve and/or sheath involvement (n = 9), apex infiltration (n = 3), and/or pachymeningitis (n = 7).CONCLUSION:Granulomatosis with polyangiitis is a rare yet potentially blinding cause of inflammatory optic neuropathy. Optic neuropathy in granulomatosis with polyangiitis may occur in the absence of systemic symptoms of disease activity and is challenging to distinguish from other inflammatory and non-inflammatory disorders affecting visual acuity. Several clinical and imaging clues suggest that optic neuropathy results from the development of an extravascular granulomatous process within the optic nerve sheath in the orbital apex, a place that is difficult to image. In a granulomatosis with polyangiitis patient with unexplained visual loss and a seemingly normal workup (fundoscopy, biology, and imaging), clinician should keep a high index of suspicion

No survival improvement in patients with high‐risk multiple myeloma harbouring del(17p) and/or t(4;14) over the two past decades

International audienceNo abstract availabl

Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review

Abstract Background Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder. A few patients develop organ complications that can be life-threatening. Our objectives were to describe the disease course and phenotype of life-threatening AOSD, including response to therapy and long-term outcome. Methods A multicenter case series of intensive care medicine (ICU) patients with life-threatening AOSD and a systematic literature review. Results Twenty patients were included. ICU admission mostly occurred at disease onset (90%). Disease manifestations included fever (100%), sore throat (65%), skin rash (65%), and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL). Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%), 10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in eight cases. Two patients died. Treatment delay was significant. All patients received corticosteroids. Response rate was 50%. As second-line, intravenous immunoglobulins were ineffective. Anakinra was highly effective. After ICU discharge, most patients required additional treatment. Literature analysis included 79 cases of AOSD with organ manifestations, which mainly included reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and cardiac complications (23%). Response rate to corticosteroids was 68%. Response rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively. Conclusions AOSD should be recognized as a rare cause of sepsis mimic in patients with fever of unknown origin admitted to the ICU. The diagnosis relies on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs should be abandoned. Long-term prognosis is favorable

Microscopic polyangiitis: Clinical characteristics and long-term outcomes of 378 patients from the French Vasculitis Study Group Registry

International audienceObjective: To describe characteristics and long-term outcomes of patients with microscopic polyangiitis (MPA), an antineutrophil cytoplasm antibody (ANCA)-associated small-vessel necrotizing vasculitis.Methods: MPA patients from the French Vasculitis Study Group Registry satisfying the European Medicines Agency algorithm were analyzed retrospectively. Characteristics at diagnosis, treatments, relapses and deaths were analyzed to identify factors predictive of death or relapse.Results: Between 1966 and 2017, 378 MPA patients (median age 63.7 years) were diagnosed and followed for a mean of 5.5 years. At diagnosis, the main clinical manifestations included renal involvement (74%), arthralgias (45%), skin (41%), lung (40%) and mononeuritis multiplex (32%), with less frequent alveolar hemorrhage (16%), cardiomyopathy (5%) and severe gastrointestinal signs (4%); mean serum creatinine was 217 μmol/L. ANCA were detected in 298/347 (86%) patients by immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA). Among the 293 patients with available ELISA specificities, 272 (92.8%) recognized myeloperoxidase and 13 (4.4%) proteinase-3. During follow-up, 131 (34.7%) patients relapsed and 78 (20.6%) died, mainly from infections. Respective 5-year overall and relapse-free survival rates were 84.2% and 60.4%. Multivariable analyses retained age >65 years, creatinine >130 μmol/L, severe gastrointestinal involvement and mononeuritis multiplex as independent risk factors for death. Renal impairment was associated with a lower risk of relapse.Conclusion: Non-renal manifestations and several risk factors for death or relapse were frequent in this nationwide cohort. While mortality was low, and mainly due to treatment-related complications, relapses remained frequent, suggesting that MPA management can be further improved

T-cell defect in Diffuse Large B-cell Lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12

International audienceIn diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear. We broadly assessed the presence and mechanisms of suppression of MDSC subsets in DLBCL. First, a myeloid suppressive signature was identified by gene expression profiling in DLBCL peripheral blood. Accordingly, we identified, in a cohort of 66 DLBCL patients, an increase in circulating G-MDSC (LinnegHLA-DRnegCD33posCD11bpos) and M-MDSC (CD14posHLA-DRlow) counts. Interestingly, only M-MDSC number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. Furthermore, T-cell proliferation was restored after monocyte depletion. Myeloid-dependent T-cell suppression was attributed to a release of interleukin-10 and S100A12 and increased PD-L1 expression. In summary, we identified expanded MDSC subsets in DLBCL, as well as new mechanisms of immunosuppression in DLBCL

Pan-HDAC Inhibitors Restore PRDM1 Response to IL21 in CREBBP-Mutated Follicular Lymphoma

International audiencePurpose: Follicular lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of follicular lymphoma cells and loss-of-function of CREBBP acetyltransferase.Experimental Design: The study used human primary cells obtained from either follicular lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches.Results: Conversely to normal B cells, follicular lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the follicular lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In follicular lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these follicular lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with follicular lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of follicular lymphoma B cells in the differentiation process.Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with follicular lymphoma through the induction of the expression of plasma cell genes

Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis

International audienc