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Introduction : Les hospitalisations pour motif infectieux en medecine interne via les urgences representent une part importante du nombre total d’hospitalisations. Les urgentistes posent un diagnostic initial qui influence le deroulement du traitement apres l'admission. Des discordances avec le diagnostic de sortie de medecine interne sont decrites dans la litterature, avec de potentielles consequences medicales et economiques. Cette etude, centree sur les patients avec un diagnostic preliminaire ou definitif d’origine infectieuse, a pour objectif principal d’evaluer le taux de discordance diagnostique entre le diagnostic evoque aux urgences et celui retenu en medecine interne. Les objectifs secondaires sont d’identifier les facteurs associes a ces ecarts de diagnostic et d’en mesurer les consequences. Materiel et Methode : Nous avons realise une etude retrospective monocentrique sur les patients hospitalises en medecine interne au Centre Hospitalier Grenoble Alpes, via un service d’urgence, du 22 mars 2021 au 22 juin 2021 inclus, avec un diagnostic evoque d’infection aux urgences et/ou retenu a la fin de leur hospitalisation en medecine interne. Nous avons determine s'il y avait une difference entre le type d’infection evoque a la sortie des urgences et le type d’infection retenu a la sortie du service de medecine interne, permettant de definir la discordance diagnostique. Les caracteristiques intrinseques des patients, liees au passage aux urgences et les caracteristiques hospitalieres de morbi-mortalite ont ete recueillies afin d’etudier leur association a la discordance diagnostique. Resultats : Sur la periode d’inclusion, 559 patients ont ete hospitalises en medecine interne, dont 280 provenaient des urgences et avaient un diagnostic infectieux retenu aux urgences et/ou en medecine interne. Il s’agissait principalement d’hommes (59,3%), avec une mediane d’âge de 80 ans, un score de Charlson superieur a 6 et une prise de 7 medicaments par jour. Une infection COVID etait le diagnostic en sortie d’hospitalisation de medecine interne chez un peu moins d’un tiers des patients inclus. Une discordance diagnostique a ete retrouvee chez 65 des 280 patients inclus soit 23,2%. Elle concernait principalement, parmi les diagnostics poses aux urgences, des diagnostics etiquetes d’origine non infectieuse (26 patients), des infections respiratoires (14 patients) et des infections urinaires (4 patients). Parmi les caracteristiques intrinseques des patients associees a une discordance diagnostique, on note un âge plus eleve (p-value 0,01) et un score de Charlson plus important (p-value 0,034). Parmi les caracteristiques du passage aux urgences, on retrouve un temps de passage plus long aux urgences (p-value 0,016). La conclusion a une infection COVID en fin d’hospitalisation de medecine interne etait associee de maniere significative a l’absence de discordance diagnostique (p-value < 0,001). Concernant l’etude de l’impact, on met en evidence une association statistiquement significative avec l’arret de l’antibiotherapie a l’arrivee dans le service (p-value < 0,0001). Conclusion : La discordance diagnostique est un probleme de sante publique qui affecte tous les services de l’hopital mais aussi la medecine ambulatoire. L’integration des connaissances actuelles dans notre pratique, ainsi que la multiplication d’etudes robustes sur la prevalence et la recherche des facteurs causals sont necessaires en vue de l’elaboration d'etudes interventionnelles.

International audience; Introduction: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disor-ders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determinedthe prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic,non-vascular neurological injury.Method: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data onpatients with acute (

Introduction Thymic epithelial tumor (TET)-associated cytopenia is rare but difficult to treat. Methods We performed a multicenter, retrospective study of TET and associated forms of cytopenia in France. Cases were collected by the French National Reference Center for Autoimmune Cytopenia and the French National Thymic Malignancy Interest Group (Reseau Tumeurs Thymiques et Cancer) and through a call for cases by the French Society of Internal Medicine. Results Thirty-six cases were recorded between 2002 and 2014 and followed up for a median of 38 months (interquartile range, 23–106 months). Thirty-two patients underwent surgery for TET, and 14 of the latter were in complete remission at last follow-up. Cytopenia can occur before, simultaneously, or after diagnosis of TET. The most common types of cytopenia were pure red cell aplasia (in 30% of cases) and Good syndrome (GS) (also in 30% of cases). Eleven patients displayed two or more episodes of cytopenia. Eighteen patients received steroids as their first-line treatment, leading to a complete response in nine. Other first-line treatments (cyclosporine and rituximab) were less effective but should be considered as treatment options. Infections developed in 84% of the patients with GS; this did not appear to be related to the presence or absence of immunosuppressive treatment or chemotherapy. Eight patients died during the follow-up period (two died of cytopenia and five of infections). Conclusions The optimal treatment for TET-associated cytopenia has not been clearly defined and the outcome does not appear to be correlated with TET progression. For GS, prophylactic immunoglobulin replacement therapy and prophylactic antibiotic therapy can be recommended.

Cystoisospora belli (previously known as Isospora belli) is a tropical coccidian parasite sometimes leading to severe diarrhea in immunocompromised patients. Here we describe a fatal case of cystoisosporiasis in a non HIV-immunocompromised 71-year-old female with no recent travel history. Infection was either latent or potentially caused by the consumption of contaminated imported food from Asia. Diagnosis was made by microscopical detection of numerous C. belli oocysts in stools without specific staining. Treatment with TMP-SMZ slightly improved diarrhea within 3days, but dehydration subsequently led to acute decompensated heart failure and a fatal evolution. This report illustrates the possibility of severe cystoisosporiasis in non HIV-immunocompromised patients in a non-endemic country and highlights the risk of transmission through imported contaminated food consumption.

International audience; Background: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.Methods: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.Results: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.Conclusions: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.

A 54-year-old male patient was admitted for acute respiratory distress with fever. He was suffering from chronic sinusitis/rhinitis and had persistent otitis for the past 2 months before admission despite several antibiotics courses. He developed a complex pulmonary involvement (embolism and diffuse alveolar hemorrhage) with acute glomerular disease (proteinuria and hematuria but initially no renal failure). Clinical suspicion of Wegener's granulomatosis was confirmed by the positive high titer of antineutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and despite a negative nasal biopsy. Treatment including cyclophosphamide and methylprednisolone intravenous pulses permitted pulmonary recovery over 4 weeks contrasting with the development of rapidly progressive glomerulonephritis and polyneuropathy of lower limbs. Renal biopsy showed pauci-immune crescentic and necrotizing glomerulonephritis. However, despite additional plasma exchanges, acute kidney injury worsened and the patient ended up in dialysis. Such a dissociated evolution was unexpected in this case since pulmonary and renal involvements reflected the same pathological process (small vessels vasculitis/capillaritis) and the same pathogenic mechanism (antiproteinase 3 autoantibodies).

Resume Introduction La maladie de Whipple est une granulomatose systemique rare et de diagnostic parfois difficile. Observation Nous rapportons une observation de maladie de Whipple dont la presentation initiale etait une encephalite aigue. La realisation de multiples prelevements a la recherche d’une maladie de Whipple a conduit au diagnostic, alors que la polymerase chain reaction (PCR) Tropheryma whipplei sur le liquide cephalorachidien etait negative et la biopsie cerebrale stereotaxique recusee. L’evolution sous antibiotherapie adaptee a ete consideree comme « spectaculaire ». Conclusion La maladie de Whipple est une cause rare d’encephalite. Le diagnostic repose sur la realisation de la PCR specifique sur divers prelevements, et sur l’histologie. L’evolution sous antibiotherapie adaptee peut etre tres favorable.

International audience; Hepatitis E virus infection - mainly genotype 3 - is increasingly common in industrialized countries. Infection is usually asymptomatic, but cases of central or peripheral neurological symptoms with hepatitis E have been described. The most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been described. In our center, since 2010, we have identified five cases of neuralgic amyotrophy associated with acute hepatitis E in immunocompetent patients. For all these patients, neuralgic amyotrophy was diagnosed with electromyogram and positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including our patients, we count 26 cases in literature. The mean age of the patients was 44 years old, with a large predominance of males (88%). The disorder is bilateral and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus were affected in 6 patients (23%). In industrialized countries, any neuralgic amyotrophy, particularly if there is bilateral, asymmetric associated with involvement of nerves outside the brachial plexus, should lead physicians to consider a diagnosis of acute hepatitis E.

Summary Background: Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. Aim: To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. Design: Cross-sectional survey. Methods: Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. Results: In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2–7.4, p50.00001) risk of discontinuation of treatment due to ADEs. Discussion: The very limited use of halofantrine indicates that the main practice recommendations of the guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.

Resume Propos. – Les meningites chroniques sont relativement rares et ne representent que 10 % de l'ensemble des meningites. Leur symptomatologie pauvre et leur evolution souvent insidieuse en font une entite mal connue. En l'absence de grande etude dans la litterature, leur prise en charge diagnostique et therapeutique est difficile. Actualites et points forts. – Si le diagnostic positif des meningites chroniques est aise, la recherche d'une etiologie repose sur une demarche particulierement difficile, les causes etant multiples, representees par des etiologies infectieuses mais egalement non infectieuses (inflammatoires, tumorales et medicamenteuses). Cette demarche diagnostique doit etre rigoureuse et orientee, afin de decider d'une therapeutique adaptee, parfois urgente. Neanmoins, malgre un bilan exhaustif, 30 % d'entre elles restent de cause indeterminee. Le clinicien est alors confronte a deux alternatives : soit choisir une attitude agressive basee sur des examens complementaires invasifs, soit adopter une position attentiste basee sur une surveillance clinicobiologique. En revanche, l'existence d'une degradation clinique en absence d'etiologie prouvee, fait parfois poser l'indication de traitements d'epreuves, mal codifies et parfois controverses. Par ailleurs, peu d'etudes sont publiees sur le pronostic et le risque evolutif d'une meningite chronique « idiopathique ». Perspectives et projets. – Apres une revue de litterature des etiologies et des moyens diagnostiques des meningites chroniques, nous proposons une attitude pratique en termes de gestion et de prise en charge therapeutique. Des lors, des etudes evaluant le suivi a long terme des meningites chroniques, notamment celle de cause indeterminee traitee ou pas de maniere empirique, pourraient optimiser leur prise en charge.

Resume Introduction La fievre Q peut mimer frequemment une maladie systemique, en induisant de nombreuses manifestations auto-immunes. Les micro-angiopathies thrombotiques sont des pathologies endotheliales, d’origine genetique ou acquise, a expression renale (syndrome hemolytique et uremique) ou neurologique (purpura thrombotique thrombocytopenique). Observation Nous rapportons l’observation d’une femme de 77 ans ayant presente une micro-angiopathie thrombotique acquise a expression renale avec presence d’anticorps anti-ADAMTS 13, survenue au cours d’une infection aigue a Coxiella burnetii . Conclusion Les manifestations auto-immunes sont frequentes dans la fievre Q mais l’existence d’anticorps anti-ADAMTS 13 responsable d’une micro-angiopathie thrombotique n’avait jamais ete decrite.

Resume Les Herpes virus sont responsables de nombreuses manifestations cliniques, incluant l’herpes genital. En depit de therapeutiques antivirales efficaces, l’herpes genital reste un probleme de sante publique. La vaccination offre la possibilite de proteger le sujet non infecte « vaccin prophylactique » ou de diminuer le nombre de recurrences cliniques et virologiques « vaccin therapeutique ». Cet article fait le point sur la recherche vaccinale actuelle, notamment sur les resultats des essais cliniques chez l’homme des vaccins sous-unites, des vaccins de type DISC et des vaccins ADN.

Systemic capillary leak syndrome (SCLS) is characterized by recurrent hypovolemic shock associated with edema, hemoconcentration and paradoxal hypoprotidemia due to leakage into the interstitial space. We report a new case with cardiac involvement. A 62-year-old man had two recurrent hypovolemic shocks with SCLS's criteria, associated twice with cardiac systolic dysfunction and atrial fibrillation. This report should enhance physician awareness of SCLS, which is a rare and severe disease, and its cardiac involvement.

Resume Le syndrome des antisynthetases constitue un sous-groupe des myopathies inflammatoires idiopathiques. Il se caracterise par une atteinte pulmonaire interstitielle, une myosite, une polyarthrite, une atteinte cutanee et la presence d’un anticorps de la famille des antisynthetases. L’atteinte pulmonaire est inaugurale dans 50 % des cas. Nous rapportons l’observation d’une femme atteinte d’un syndrome des antisynthetases, revele de maniere brutale, sous forme d’un syndrome de detresse respiratoire aigue. Cette patiente, suivie pour une sclerodermie, pose la question d’un possible syndrome de chevauchement. L’interet de cette observation reside egalement dans l’obtention d’une amelioration sous anti-CD20.

Conventional polymerase chain reaction (PCR) in respiratory samples does not differentiate between Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii (Pj) colonization. We used Pj real-time quantitative PCR (qPCR) with the objective to discriminate PCP from Pj colonization in immunocompromised patients. All positive Pj qPCR [targeting the major surface glycoprotein (MSG) gene] obtained in respiratory samples from immunocompromised patients presenting pneumonia at the Grenoble University Hospital, France, were collected between August 2009 and April 2011. Diagnoses were retrospectively determined by a multidisciplinary group of experts blinded to the Pj qPCR results. Thirty-one bronchoalveolar lavages and four broncho aspirations positive for the Pj qPCR were obtained from 35 immunocompromised patients. Diagnoses of definite, probable, and possible PCP, and pneumonia from another etiology were retrospectively made for 7, 4, 5, and 19 patients, respectively. Copy numbers were significantly higher in the “definite group” (median 465,000 copies/ml) than in the “probable group” (median 38,600 copies/ml), the “possible group” (median 1,032 copies/ml), and the “other diagnosis group” (median 390 copies/ml). With the value of 3,160 copies/ml, the sensitivity and specificity of qPCR for the diagnosis of PCP were 100 % and 70 %, respectively. With the value of 31,600 copies/ml, the sensitivity and specificity were 80 % and 100 %, respectively. The positive predictive value was 100 % for results with more than 31,600 copies/ml and the negative predictive value was 100 % for results with fewer than 3,160 copies/ml. qPCR targeting the MSG gene can be helpful to discriminate PCP from Pj colonization in immunocompromised patients, using two cut-off values, with a gray zone between them.

Resume Dans cette etude prospective multicentrique, 151 dossiers ont ete etudies. Dans 138 cas le dossier etait rempli pour une suspicion clinique de listeriose. Dans 16 % des cas, le diagnostic etait confirme par la bacteriologie, dans 17 % des cas, le diagnostic etait probable, dans 60 % il s'agissait de diagnostic differentiel. Dans 13 cas le diagnostic etait uniquement bacteriologique sans evocation clinique. La suspicion d'infection a Listeria etait faite par le terrain sous-jacent dans 100 cas sur 138; les tableaux neurologiques et le syndrome grippal chez la femme enceinte etaient les situations cliniques faisant evoquer le plus souvent le diagnostic. Les difficultes diagnostiques residaient chez l'immunodeprime et le sujet âge ou la fievre etait alors le seul signe d'appel. Lorsque le diagnostic etait evoque, l'antibiotherapie etait toujours correctement instauree.

International audience; OBJECTIVES: This study aims at describing the evolution of the epidemiology of invasive aspergillosis (IA) in a French University Hospital focussing on nosocomial cases, in order to assess the efficiency of the environmental preventive measures which were implemented. METHODS: From 2003 to 2009, IA cases were reviewed monthly and classified according to the EORTC/MSG criteria and the origin of contamination. RESULTS: Five proven and 65 probable IA cases were diagnosed. Most of the cases (74.3%) occurred in patients with haematological malignancies. Incidences of IA and nosocomial IA (NIA) were 0.106 and 0.032 cases per 1000 admissions, respectively. All the 21 NIA cases occurred in the absence of air treatment (laminar air flow facilities or Plasmair decontamination units) and/or during construction works. The 3-month and 1-year overall survival rates were 50.6% [38.2-61.7] and 31.1% [20-42.9] respectively, and did not differ according to the origin of contamination. CONCLUSION: Nosocomial IA still accounted for a third of all IA cases diagnosed from 2003 to 2009 and mainly occurred in the absence of environmental protective measures, which were confirmed to be effective when applied. Our results show that extension and/or reinforcement of these measures is needed, especially in the haematology unit and during construction works.

Hemolysis is a rare complication of cytomegalovirus infection in the immunocompetent adult, and the mechanisms responsible for it remain obscure. Guidelines for treatment have yet to be established, and the effectiveness of antiviral therapy has not been proven. In this report, an unusual case of primary cytomegalovirus infection manifested by severe hemolysis in an immunocompetent adult is presented. Treatment with ganciclovir (5 mg/kg b.i.d.) for 10 days and prednisolone (2 mg/kg/day) for more than 3 months suggests that both virological and immunological mechanisms are probably responsible for the hemolysis.