Etude sur les manifestations neurologiques centrales du syndrome de Gougerot-Sjögren, corrélations des explorations neuropsychologiques de l'imagerie par résonance magnétique et de la scintigraphie de perfusion au 99mTC-éthyl cystéinate dimer (ECD)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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

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

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

Catastrophic adult-onset Still’s disease as a distinct life-threatening clinical subset: case–control study with dimension reduction analysis

International audienceObjectives: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset. Methods: We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD). Results: Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation. Conclusion: This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still's disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy

Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides

International audienceObjective - To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. Methods - The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed. Results - Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time. Conclusion - The rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival. Trial registration number - NCT00748644