Objective. To describe a population of patients with symptomatic cryoglobulinaemia, comparing manifestations and outcome as a function of hepatitis C virus (HCV) status. Patients and methods. A ...retrospective study on 179 patients who tested positive for cryoglobulins, seen between 1978 and 1998 in an internal medicine department. Results. Among 179 cryoglobulin‐positive patients, only 49 (18 men, 31 women; mean age 59.96±12 yr) had clinical manifestations attributable to cryoglobulinaemia. Thirty‐three had HCV infection, 20 had systemic autoimmune diseases, two had haematological diseases, one had human immunodeficiency virus and HCV co‐infection, one had HCV and HBV co‐infection and six had essential mixed cryoglobulinaemia. The clinical manifestations and cryoglobulin levels in HCV+ and HCV− patients did not differ significantly. Only arthralgias and elevated transaminases were significantly more frequent in HCV+ patients (P<0.02 and <0.05, respectively). Five‐year survival rates were comparable for HCV+ and HCV− patients. Eight patients died (six HCV+, two HCV−), with a median time between diagnosis and death of 38.7 months. Conclusion. Clinical manifestations of cryoglobulinaemia, except arthralgias, were comparable for HCV+ and HCV− patients. When systemic manifestations are present, the prognosis is poor despite intensive or prolonged therapy.
Churg-Strauss syndrome (CSS) is a systemic vasculitis characterized by the presence of asthma, hypereosinophilia, and necrotizing vasculitis with extravascular eosinophil granulomas. In this ...retrospective study of 96 patients between 1963 and 1995, we analyzed clinical manifestations, identified prognostic factors, and assessed the long-term outcome. CSS was diagnosed when asthma, hypereosinophilia > 1,500/mm3 or > 10%, and clinical manifestations consistent with systemic vasculitis, with or without histologic evidence, were present. Asthma was the most frequently observed manifestation at presentation, with mononeuritis multiplex the second. Other common manifestations were weight loss, fever, myalgia, skin involvement, paranasal sinusitis, arthralgia, pulmonary infiltrate, and gastrointestinal involvement. Mean eosinophilia at presentation was 7.193 +/- 6.706/mm3; ANCA, present in 20 of 42 (47.6%) patients, predominantly gave the perinuclear labeling pattern. All the patients were treated with corticosteroids alone or in combination with cyclophosphamide or plasma exchanges. Clinical remission was obtained in 91.5%; 22 (25.6%) patients relapsed. Twenty-three patients died during follow-up: 11 of these deaths were directly due to vasculitis. The presence of severe gastrointestinal tract or myocardial involvement was significantly associated with a poor clinical outcome. The long-term prognosis of CSS is good and does not differ from that of polyarteritis nodosa, although most patients need low doses of oral corticosteroids for persistent asthma, even many years after clinical recovery from vasculitis.
Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from ...clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans.
The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 95% confidence interval (CI), 1.2-4.9), high (>1:512) serum antigen titre (OR, 2.6 1.3-5.4), and lack of flucytosine during induction therapy (OR, 3.8 1.9-7.8). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy.
Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.
Objectives
The aim of this study was to describe the proportion of liver‐related diseases (LRDs) as a cause of death in HIV‐infected patients in France and to compare the results with data from our ...five previous surveys.
Methods
In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV‐infected patients who were regularly followed up. Results were compared with those of previous cross‐sectional surveys conducted since 1995 using the same design.
Results
Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus (HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/μL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver‐related causes of death, the proportion represented by hepatocellular carcinoma (HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019).
Conclusions
The proportion of LRDs among causes of death in HIV‐infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995−2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus (HCV) coinfection, HCC representing almost half of liver‐related causes of death.
Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three ...serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates.
Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multiplication and high genomic differences, confirming the possible speciation of serotypes A and D. Furthermore, we observed a better prognosis for infections caused by AD hybrid than those caused by serotype A or D, at least for those diagnosed in France.
La sarcoïdose est une granulomatose diffuse, atteignant préférentiellement le thorax. Les manifestations neurologiques surviennent dans seulement 5 à 6 % des cas. Nous rapportons deux observations de ...neurosarcoïdose, dont l’originalité repose sur la mise en évidence dans un premier cas d’une atteinte histologique de localisation temporale, hippocampique gauche et cérébelleuse vermienne et dans le deuxième cas, une poussée de sarcoïdose caractérisée par une localisation neurologique centrale du cône terminal de la moelle épinière révélée par un syndrome de la queue de cheval.
Observation 1 : un patient, âgé de 57 ans, a présenté des troubles de la déglutition transitoires associés à des troubles de l’équilibre et des épisodes confusionnels. L’évaluation clinique n’a pas trouvé d’hépato-splénomégalie, pas d’adénopathie périphérique. La peau était calme, les articulations étaient indolores. Il n’y avait pas d’hypertrophie franche des glandes parotides ou sous maxillaires. L’IRM cérébrale a montré des hypersignaux FLAIR du lobe temporal gauche, hippocampique gauche et de la région cérébelleuse vermienne. Un TEP scanner effectué retrouvait l’hypermétabolisme cérébral concordant avec les lésions visibles en IRM. Le TEP scanner dans sa description n’a pas montré de rehaussement particulier des glandes salivaires parotidiennes ou sous maxillaires ni des globes oculaires. La ponction lombaire a été acellulaire avec une protéinorachie isolée. L’ensemble des PCR virales est resté négatif ainsi que la PCR BK. Le dosage d’enzyme de conversion était normal dans le sérum. Une biopsie des glandes salivaires accessoires dans l’hypothèse d’un neuro Sjögren mettait en évidence une sialadénite lymphocytaire aspécifique. Il n’avait pas de signe extra neurologique associé lors de l’installation de ce tableau dont le diagnostic de neurosarcoïdose a été porté par une biopsie cérébrale. L’aggravation des troubles de déglutition a conduit le patient en réanimation pour une pneumopathie d’inhalation et le lavage bronchioloalvéolaire effectué en contexte infectieux n’était pas contributif. Une trachéotomie a été mise en place pendant toute la période réanimatoire. La corticothérapie initiée par bolus a été reliée à 80mg/jour sans traitement adjuvant associé. L’évolution clinique a été marquée par une amélioration de la déglutition. Enfin, l’IRM de contrôle effectuée à 3 mois du début du traitement et du diagnostic retrouvait une amélioration très nette des hypersignaux FLAIR et la persistance dans la partie tout antérieure du lobe temporal gauche et de la région hyppocampique gauche d’anomalies de signal modérées. Le traitement corticoïde était arrêté au bout de 5 ans de suivi et le patient a gardé une ataxie cérébelleuse séquellaire permettant néanmoins la marche avec déambulateur, et une surdité totale non appareillable. Observation 2 : un patient, âgé de 52 ans, a présenté un tableau clinique de syndrome de la queue de cheval (déficit sensitivomoteur des membres inférieurs et des troubles sphinctériens). L’examen n’a pas trouvé de signes respiratoires ou cutanés. La ponction lombaire a révélé une méningite lymphocytaire hyperprotéinorachique hypoglycorachique avec PCR BK négative. L’électromyogramme a objectivé une atteinte polyradiculaire lombosacrée latéralisée à droite. L’IRM dorsolombosacrée a trouvé des nodules arachnoïdiens au niveau de la partie postérieure du cône terminal et des racines de la queue de cheval. Le scanner thoracique mettait en évidence des adénopathies médiastinales bilatérales. Le lavage bronchioloalvéolaire a trouvé une alvéolite lymphocytaire à prédominance de CD4 (70 %). L’enzyme de conversion de l’angiotensine était positive dans le LCR mais négative dans le sang. Une biopsie ganglionnaire sous médiastinoscopie a révélé une granulomatose gigantocellulaire et épithélioïde non nécrosante. Après initiation d’une corticothérapie par 3 boli de solumedrol, 3jours de suite puis prednisone orale 1mg/kg/j. L’évolution était marquée par une franche amélioration des signes sensitifs et du déficit moteur. La marche était possible avec steppage séquellaire du membre inférieur droit et l’IRM médullaire a montré une quasi-normalisation des signes de la queue de cheval.
La neurosarcoïdose inaugurale est un mode de révélation rare et de diagnostic difficile de la sarcoïdose. Elle peut être inaugurale sans signes systémiques associés. L’IRM est la technique d’exploration de référence dans la prise en charge initiale et l’orientation diagnostique, mais aussi dans le suivi évolutif sous traitement de ces patients.
We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three ...hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk RR 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present), mortality was 25.9% (p < 0.005); when FFS > 2 (3 or more of the 5 factors present), mortality was 45.95% (p < 0.0001 between 0 and 2, p < 0.05 between 1 and 2). We conclude that an initial assessment of PAN or CSS severity enables outcome and mortality to be predicted. The FFS is a good predictor of death and can be used to help the clinician choose the most adequate treatment. Renal and GI signs are the most serious prognostic factors.
Objectives To describe HIV-1 variants circulating in Mali and to estimate the rate of transmission of HIV-1 drug resistance in 2006. Patients and methods Viral reverse transcriptase (RT) and protease ...(PR) genes from 198 antiretroviral (ARV)-naive patients diagnosed HIV-1 positive in May 2006 in Bamako and Segou were sequenced. Results Although CRF02_AG was always the predominant HIV-1 subtype observed (72%), a higher genetic diversity than that in 2005 was observed. The overall prevalence of primary resistance is 11.5% in Mali in 2006, according to the 2007 IAS-USA list of mutations nucleoside RT inhibitor (NRTI): 1.5%, non-NRTI (NNRTI): 9% and PI: 1%, and 2.5% (NRTI: 1%, NNRTI: 1.5% and PI: 0%), according to the Stanford list of mutations. There was no significant difference between 2005 and 2006 in the overall primary resistance prevalence or in the prevalence of mutations in the different ARV classes. Resistance mutations found in RT and PR genes are in agreement with the highly active antiretroviral therapy regimen available in Mali, except for V90I, V106I and A98G mutations which are associated with etravirine resistance, but polymorphic in non-B subtypes. Conclusions HIV-1 genetic diversity seems increased in Mali, but the overall HIV-1 primary resistance prevalence remains low. This is consistent with the findings from other West African countries where prevalence rates are lower than 5%. However, considering the large scaling up of ARV use in this country, it is necessary to regularly monitor the development of primary resistance in Mali.
Background
More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end‐stage liver disease (ESLD) in ...HIV‐infected adults in France between 1995 and 2005.
Design and methods
In 2005, 34 departments prospectively recorded all deaths in HIV‐infected patients who were followed in those departments (around 24 000). Results were compared with those of four previous cross‐sectional surveys conducted since 1995 using the same methodology.
Results
Among 287 reported deaths in 2005, 100 (35%) were related to AIDS, and 48 (17%) to ESLD. Three out of four patients who died from ESLD‐related causes had chronic hepatitis C. Excessive alcohol consumption was reported in approximately half of the patients (48%). At death, 62% of patients had undetectable HIV viral load and the median CD4 count was 237 cells/μL. From 1995 to 2005, the proportion of deaths caused by ESLD increased from 2 to 17% (P<0.001). The proportion of deaths caused by hepatocellular carcinoma increased from 5% in 1995 to 25% in 2005 (P=0.0337).
Conclusions
Over the 10 years from 1995 to 2005, the proportion of deaths caused by hepatitis C virus‐related ESLD has increased in HIV‐infected patients. ESLD is currently a leading cause of death in this population, with hepatocellular carcinoma representing a quarter of liver‐related deaths. Recommendations for the detection of hepatocellular carcinoma should be strictly applied in these patients.
PDF
