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Resume Introduction La sarcoidose est une granulomatose systemique sans etiologie connue, touchant rarement le tube digestif. Observation Une femme de 54 ans consultait pour des douleurs epigastriques et de l’hypochondre droit evoluant depuis plusieurs mois associees a des vomissements responsables d’une perte de poids importante. Les explorations retrouvaient des adenopathies retroperitoneales non compressives avec granulomes epithelioides et gigantocellulaires sans necrose caseeuse a l’examen anatomo-pathologique, compatibles avec une sarcoidose. La localisation duodenale n’etait retrouvee qu’a la troisieme gastroscopie. La corticotherapie entrainait une amelioration rapide. Conclusion Une localisation digestive de la sarcoidose doit etre evoquee chez un patient ayant des troubles digestifs et une sarcoidose avec d’autres localisations. Les gastroscopies doivent etre repetees pour permettre le diagnostic et le traitement permet le plus souvent une amelioration clinique franche et rapide.

International audience; The aim of this study was to estimate influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza among hospitalized patients. A case-control investigation was based on the prospective surveillance of influenza-like illness (ILI) during five flu seasons. We compared influenza-positive cases and influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season (11%; 95% CI -232% to 76%) when the vaccine and circulating viruses were mismatched. Expansion of the study to other hospitals could provide IVE estimates earlier in the season, for different age groups and emerging virus strains.

Hereditary fibrinogen A -chain amyloidosis: Phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 115: 2998–3007, 2010 Arie J. Stangou, Nicholas R. Banner, Bruce M. Hendry, Mohamed Rela, Bernard Portmann, Julia Wendon, Mark Monaghan, Philip MacCarthy, Muriel Buxton-Thomas, Christopher J. Mathias, Juris J. Liepnieks, John O’Grady, Nigel D. Heaton, and Merrill D. Benson Fibrinogen amyloidosis due to mutations in the fibrinogen -chain gene (AFib) localized on chromosome 4 and composed of six exons belongs to the group of nonneuropathic hereditary renal amyloidoses. It is the most common type of all hereditary renal amyloid diseases in the United States and Europe. Like other forms of amyloidosis, AFib amyloidosis is a protein misfolding disorder. Fibrinogen production is exclusively hepatic. Liver transplantation was therefore considered as a logical mode of treatment, whereas isolated renal transplantation was followed by kidney amyloid recurrence in most patients. Stangou et al. have first revisited the current phenotypic description of AFib amyloidosis and second performed a systematic evaluation for liver and kidney transplantation (LKT) in a series of 22 patients (8 women, 14 men). Three of them had been misdiagnosed as primary systemic AL amyloidosis—a diagnostic error already reported (1). The median age at presentation was 55 years (range 33 to 63 years). Proteinuria was the most common presenting feature (median 24-hour urine protein 7.2 g; range 0 to 11.8 g). At the time of assessment, median GFR was 16 ml/min (range 0 to 52 ml/min). Renal biopsy was performed in 21 of 22 patients and revealed amyloidosis in all patients, with enlarged glomeruli replaced by amyloid with minimal or no extraglomerular involvement—a finding suggestive of this type of amyloidosis (1). Twenty of 22 patients progressed to ESRD. Two patients had liver amyloidosis, complicated in one by end-stage liver disease. Coronary atherosclerotic disease was documented in 15 patients (68%), in half of the patients predating evolution of kidney impairment. Twelve patients had severe systemic vascular disease, involving aorta, splanchnic, or carotid arteries. Two patients underwent carotid endarterectomy. Of interest, the excised material contained amyloid purely consistent of mutant fibrinogen A -chain. Cardiac amyloidosis was not a rare localization. Echocardiography was abnormal in 11 of 21 patients (52%). Three of the four endomyocardial biopsies revealed substantial amyloid deposition. One patient developed dilated amyloid cardiomyopathy in association with coronary disease and myocardial amyloidosis, whereas cardiac amyloidosis usually leads to restrictive cardiomyopathy. In addition, cardiac parasympathetic dysfunction and risk of bradycardia were identified in 12 patients. Seven of them had pacemaker insertion. Autonomic involvement of the gastrointestinal tract was a feature in 15 patients. Only 24% of patients had family history of renal disease. However, 81% had family history of systemic or coronary vascular disease. Family members who had such cardiovascular history were indeed carriers of AFib mutations. Spontaneous splenic rupture occurred in four patients (one during hemodialysis and three during transplantation). The excised spleen contained widespread amyloid. Nine of 14 patients accepted on the waiting list received combined liver and kidney allografts. At a median follow-up of 67 months, six of nine patients are alive and well with normal liver function. Five patients have good renal function. Cardiac amyloidosis has not progressed after LKT. I-labeled serum amyloid P component (SAP) scintigraphy showed regression of systemic visceral amyloid deposits as early as at the first annual follow-up scan after LKT, whereas scintigraphy documented progressive amyloid deposition in two patients who had previously undergone isolated kidney transplant. Serial 99mTcDMSA renal scintigraphy after preemptive LKT in two patients demonstrated stable native renal uptake. Four patients with various liver diseases received, after full information, explanted livers from AFib patients. Only one “domino” recipient had SAP scans and echocardiography for up to 5 years with no evidence of de novo amyloid deposition. The study by Stangou et al. extends the clinical scope of AFib amyloidosis. Stangou et al. encourage evaluation of isolated liver transplant early in the course of amyloid nephropathy to prevent systemic deposition and renal progression to ESRD. Amyloid fibrils in AFib contain exclusively variant fibrinogen. Circulating total fibrinogen consists of a mixture of wild-type/ variant fibrinogen in a ratio of 1:1 to 3:2. Wild-type fibrinogen does not perpetuate amyloid disease. After liver transplant, the variant fibrinogen is eliminated and promptly replaced by Published online ahead of print. Publication date available at www.cjasn.org.

Treatment of hepatitis C (HCV)–mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m2) once a week for 1 month followed by Peg-interferon-α (Peg-IFN-α; 2a, 180 μg or 2b, 1.5 μg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-α/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-α/ribavirin, rituximab plus Peg-IFN-α/ribavirin–treated patients had a shorter time to clinical remission (5.4 ± 4 vs 8.4 ± 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69+ B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-α/ribavirin is well tolerated and more effective than Peg-IFN-α/ribavirin in HCV-MC.

Alveolar echinococcosis (AE) is a rare but potentially serious zoonosis for which an early diagnosis is of primary importance. We report the first observation of AE in a cardiac transplant patient infected by hepatitis C virus. He first presented with a single asymptomatic hepatic nodule. The liver biopsy showed an epithelioid granuloma with necrosis. We review the clinical features, diagnosis and outcome of this disease in immunocompromised hosts. In immunocompromised patients living in areas endemic for Echinococcus multilocularis, AE should be included in the differential diagnosis of tumor like lesions of the liver.

Objective To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV)–related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG–IFN alfa-2b) plus ribavirin. Methods The study group comprised 32 HCV RNA–positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG–IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone. Results Treatment with rituximab and PEG–IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean ± SD followup period of 23 ± 12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall. Conclusion Rituximab is an effective treatment of severe and/or refractory HCV-related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy.

Virus-associated hemophagocytic syndrome (VAHS) is a rare complication in early cytomegalovirus (CMV) infection. There is no standard therapy for VAHS and the clinical course is variable. Data on the use of intravenous immunoglobulin (IVIG) in the treatment of CMV-associated VAHS are limited. We report a previously healthy, 32-year-old woman who presented with general malaise, fever, chills, and splenomegaly. Laboratory examination showed marked elevation of aminotransferase, leucopoenia, and thrombocytopenia. Acute CMV-infection was documented by the presence of immunoglobulin M anti-CMV and positive viremia in blood sample. Bone marrow examination revealed extensive hemophagocytosis. IVIG was administered after the diagnosis of CMV-associated VAHS. Her symptoms and laboratory abnormalities improved dramatically after the onset of the treatment and she did not require antiviral agent.

Resume Introduction L'utilisation des essais de non-inferiorite est de plus en plus frequente dans la validation des traitements anticoagulants. Un essai de non-inferiorite consiste a montrer que deux traitements ne sont pas trop differents, et que cette difference reste inferieure a un seuil prealablement fixe. Ce seuil correspond a la quantite d'efficacite que l'on peut consentir a perdre, etant donne les autres avantages du nouveau traitement. L'objectif de ce travail est de faire une etude descriptive des essais de non-inferiorite realises jusqu'a present, dans le cadre de la maladie thromboembolique veineuse, en se focalisant sur la determination des seuils de non-inferiorite utilises. Methode Nous avons identifie les essais de non-inferiorite publies dans la maladie thromboembolique veineuse par une recherche systematique sur PubMed. Nous avons calcule la perte d'efficacite consentie en nous referant a la valeur de l'efficacite minimale demontree du traitement de reference contre placebo. Resultats Nous avons trouve neuf essais de non-inferiorite portant sur la maladie thromboembolique veineuse. La perte d'efficacite maximale toleree etait en moyenne de 434 % avec une mediane a 357 %. Pour 85 % des valeurs, la perte d'efficacite consentie est superieure a 100 %. Discussion Les trois quarts des essais de non-inferiorite dans la maladie thromboembolique concluent a l'equivalence alors qu'il existe une perte d'efficacite potentielle de la totalite de l'effet du traitement standard par rapport au placebo. Les resultats des essais de non-inferiorite doivent donc etre interpretes avec prudence. Le choix du seuil de non-inferiorite doit etre plus rigoureux et etre positionne par rapport a l'efficacite minimale demontree du traitement de reference.

Churg-Strauss syndrome (CSS) is an extremely rare disease, and even less common in women of childbearing age. Patients with severe disease or those who are un-responsive to corticosteroids are usually treated with cytotoxic drugs, especially cyclophosphmide. Intravenous immunoglobulin (IVIg) has became a promising, but not completely accepted, form of treatment for systemic vasculitis that is un-responsive to standard therapy. We report a case of a woman who presented with a CSS flare during pregnancy. Because of mono-neuritis, treatment with IVIg was instituted with successful results. Our case not only supports the beneficial effect of IVIg in CSS, but it also illustrates its successful and safe use in a patient who was pregnant. We discuss the indication of IVIg during the course of anti-neutrophil cytoplasm antigen (ANCA) vasculitis during the pregnancy.

Introduction L’hematopoiese extra-medullaire est une affection rare correspondant au developpement ectopique de tissu hematopoietique en dehors de la moelle osseuse en reponse a une hyperstimulation medullaire. Il s’agit d’un mecanisme compensateur lie a la production insuffisante de cellules sanguines par la moelle osseuse, ou a la destruction de celles-ci en cas d’hemolyse chronique dans un contexte de thalassemie ou de spherocytose hereditaire, rarement de drepanocytose. Ce phenomene survient principalement dans des sites d’hematopoiese embryonnaires (rate, foie, ganglions lymphatiques), parfois dans d’autres organes comme les reins, les poumons et le tube digestif. La localisation surrenalienne est inhabituelle. Observation Un volumineuse masse surrenalienne droite avec insuffisance surrenalienne peripherique a ete decouverte chez une femme de 28 ans suivie pour une drepanocytose homozygote SS. Le bilan radiologique (scanner et scintigraphie aux colloides marques) etait en faveur d’un foyer d’hematopoiese extra-medullaire. Devant l’augmentation progressive et symptomatique de la taille de la lesion, une surrenalectomie a ete realisee avec un examen histologique qui confirmait ce diagnostic. Conclusion Notre observation decrit un cas exceptionnel d’hematopoiese extra-medullaire surrenalienne chez une patiente drepanocytaire. Le diagnostic doit etre evoque devant une masse surrenalienne sur un terrain d’hemoglobinopathie.

Introduction Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have already been achieved using rituximab in hepatitis C virus-positive immunocompetent patients. Conversely, to the best of our knowledge there are no reports in the literature regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia. Case presentation We report here the case of a 60-year-old Caucasian man who presented with hepatitis B virus-associated type II cryoglobulinemia with severe multisystem disease, including membranoproliferative glomerulonephritis with acute renal failure. The vasculitis was refractory to conventional and antiviral therapy but rituximab use led to a fall in cryoglobulin levels and disease control. The B-cell depletion was safe and efficient to induce a complete remission of the disease. Conclusion Our case highlights the benefit and the efficacy of rituximab in association with antiviral therapy in small vessel vasculitis related to hepatitis B virus-associated mixed cryoglobulinemia.

Gammacarboxyglutamic acid (gla) is a non essential amino acid synthesized in presence of vitamin K, predominantly found in coagulation and bone proteins. In 14 cases of deep vein thrombosis and in 11 cases of disseminated intravascular coagulation, compared to 19 normal subjects and 9 patients hospitalized for leg pain, free plasma gla levels were found significantly elevated (respectively 372 +/- 244 and 559 +/- 361 versus 146 +/- 34 and 120 +/- 40 pmol/mL). In six paired plasma and serum, gla levels were similar. These results suggest an involvement of blood coagulation in gla generation with need of a catabolism of the activated factors. A significant decrease was noticed during vitamin K antagonist therapy and liver disease, both instances in which the synthesis of gla containing coagulation factors is affected. During hepatocellular carcinoma with elevated desgamma carboxyprothrombin, gla was found normal, denying an global impairement of the vitamin K metabolism.

We report the case of a 36 year old woman who presented a renal cell carcinoma, associated to a membranous nephropathy as a paraneoplastic syndrome. The concomitant association with a splenic hamartoma was probably fortuitous. Five years after nephrectomy, the patient was asymptomatic and her proteinuria was very low. We studied in the literature 93 cases which reported a such association between cancer, nephrotic syndrome and membranous nephropathy. Carcinoma of the lung and adenocarcinoma of the gastrointestinal tract are the most frequently implicated. This association can occur at every age and more often in men (75%) than in women. The survival is directly linked to the evolution of the cancer. Proteinuria and membranous nephropathy can totally disappear after surgical resection of the carcinoma. The glomerular injury is mediated by immune complexes composed at least in part of tumour associated antigens. The development of several types of glomerular injury in patients with carcinoma have been described but membranous glomerulonephritis is the most commonly observed.