Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2

PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Treatment of hepatitis C-related kidney disease

Introduction: Hepatitis C virus (HCV) infection has been associated with a large spectrum of glomerular lesions in both native and transplanted kidneys. The most common HCV-associated renal disease is type I membranoproliferative glomerulonephritis usually, but not invariably, in the context of type II mixed cryoglobulinemia (MC). HCV infection is also the major cause of MC, a systemic vasculitis characterized by involvement of small and, less frequently, medium-sized vessels. Conflicting data exist on the treatment of HCV-associated glomerular disease.

Areas covered: This review examines the drugs used for management of HCV-related kidney disease and discusses current and new strategies. All literature concerning treatment of HCV-associated kidney disease has been retrieved by electronic (Medline) and manual searches.

Expert opinion: Various approaches have been recommended for the treatment of HCV-related glomerular disease, including immunosuppressive therapy (corticosteroids, cytotoxic agents and mAbs) and antiviral therapy. These regimens should be considered according to the level or proteinuria and kidney failure. Immunosuppressive agents are recommended in patients with nephrotic syndrome and/or rapidly progressive kidney failure. Antiviral treatment based on IFN and/or ribavirin or triple antiviral therapy (PEGylated-IFN/ribavirin/telaprevir or boceprevir) has been adopted in patients with moderate proteinuria and slow loss of kidney failure; however, the number of patients enrolled was small. Some patients with HCV-related cryoglobulinemic glomerulonephritis have been treated with rituximab but some issues about its role remain to be clarified. The antiviral treatment of HCV-related glomerular disease is expected to improve in the near future with new agents provided with greater efficacy and safety. However, the affordability of these drugs remains a pivotal issue, particularly in low-income countries.     

AL cardiac amyloidosis and arterial thromboembolic events

OBJECTIVE: To study the prevalence and characteristics of arterial thromboembolic events (ATEE) in the course of AL amyloidosis. METHODS: We report the case of a non-anticoagulated patient with AL amyloidosis restrictive cardiomyopathy who developed acute lower limb ischaemia. We then prospectively determined the prevalence of ATEE in all patients with AL amyloidosis who were evaluated in our institution for autologous peripheral stem cell transplantation. RESULTS: Nine out of 15 non-anticoagulated patients (60%) developed ATEE: ischaemic stroke (3), transient cerebral ischaemic attack (2), multiple peripheral arterial emboli (1), bilateral iliac artery thrombosis (1), bilateral optic nerve ischaemia (1), and mesenteric ischaemia (1). Haemodynamic stasis seemed to play a leading role in the pathophysiology of ATEE, in that all patients were on sinus rhythm and only one had a thrombus on echocardiography. We identified possible contributing factors to ATEE occurrence: concomitant treatments with oestroprogestogen regimen, thalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and extracellular volume disturbances related to the cytapheresis procedure. CONCLUSION: We report on an unusual frequency of ATEE among patients with AL cardiac amyloidosis. Despite its theoretical risks, anticoagulation should be discussed for patients with amyloid cardiomyopathy.     

Hepatitis C virus infection and lymphoproliferative diseases: prospective study on 1,576 patients in France

CONTEXT: Discordant data have been reported about the prevalence of hepatitis C virus (HCV) infection in patients with lymphoproliferative diseases and the putative role of HCV in lymphomagenesis. OBJECTIVE: To assess the prevalence of HCV infection in patients admitted to a hematology department in Paris, France. DESIGN: Prospective, controlled study. SETTING: University medical center. PATIENTS: 813 patients admitted to the Hematology department (164 B-cell non-Hodgkin's lymphoma, 34 Hodgkin's diseases, 107 chronic lymphocytic leukemia, 54 multiple myeloma, 12 Waldenstr?m's macroglobulinemia, 17 acute lymphoblastic leukemia, 6 hairy cell leukemia, 189 myeloproliferative diseases, 6 solid organ tumors, and 224 nonmalignant diseases) and 694 patients admitted to the Internal Medicine department (control group). MEASUREMENTS: All patients were tested for antibodies to HCV by a third-generation enzyme-linked immunosorbent assay. RESULTS: HCV antibodies were detected in 20 of 813 (2.46%) patients in Hematology including 11 of 394 (2.79%) patients with lymphoproliferative diseases, 3 of 164 (1.83%) B-cell non-Hodgkin's lymphoma, 2 of 107 (1.87%) chronic lymphocytic leukemia, 1 of 54 (1.85%) multiple myeloma, 1 of 189 (0.5%) myeloproliferative diseases, and 8 of 224 (3.57%) nonmalignant hematologic diseases. HCV antibodies were detected in 3 of 694 (0.43%) patients in the control group. HCV contamination preceded B-cell non-Hodgkin's lymphoma only in 2 of 3 HCV-positive patients. CONCLUSION: The prevalence of HCV infection was low (1.83%) in patients with B-cell non-Hodgkin lymphoma. HCV seems not to play a major role in the pathogenesis of B-cell lymphoma in France. Cofactors should be stressed to explain geographical discrepancies.     

Comparison of non-invasive liver fibrosis biomarkers in HIV/HCV co-infected patients: the fibrovic study--ANRS HC02

BACKGROUND/AIMS: To compare non-invasive biological liver fibrosis scores, as alternatives to liver biopsy, in HIV/HCV co-infected patients. METHODS: Two hundred and seventy-two HIV/HCV patients, nai ve for HCV treatment, underwent liver biopsy [197 (72%) men, 39.9 years, fibrosis stage (Metavir) F1 (25%), F2 (40%), F3 (25%), F4 (10%), median CD4 486/mm(3) and median HIV viral load 3.5log. Fibrotest (FT), Hepascore (HS), Fibrometer (FM), SHASTA, APRI, Forns index, and Fib-4 were tested in order to differentiate patients with mild to moderate fibrosis (F2) and those with advanced fibrosis (F3). The AUROC and the rate of well-classified patients were compared to liver biopsy. RESULTS: FT, HS, and FM were able to stage liver fibrosis in all patients with AUROCs of 0.78, 0.84 and 0.89 for the diagnosis of F2, respectively. The correlation coefficient indexes were 0.37, 0.46 and 0.48, respectively. The rates of well-classified patients were 62%, 68% and 71%, respectively. Fib-4, APRI and the Forn's index were only able to stage 37-61% of patients and showed lower accuracies. Using a combination of FT, HS and FM did not significantly increase the performance of each test. CONCLUSIONS: In HIV/HCV co-infected patients, Fibrometer, Hepascore and Fibrotest outperformed other non-invasive liver fibrosis biomarkers for the prediction of significant liver fibrosis.     

Treatment of hepatitis C virus in human immunodeficiency virus infected patients in "real life": modifications in two large surveys between 2004 and 2006

BACKGROUND/AIMS: To analyze the barriers to HCV treatment in HIV-HCV co-infected patients and their evolution between 2004 and 2006. METHODS: Three hundred and eighty HIV-HCV co-infected patients were prospectively included in surveys from November 22 to 29, 2004 (2004 survey), and 416 from April 3 to 10, 2006 (2006 survey). RESULTS: Patients in 2006 compared to those in 2004 had negative HCV RNA more often (24% vs. 12%). The rate of liver biopsy was similar (56% vs. 54%) while 24% had had a non-invasive liver damage assessment. The rate of previous treatment for HCV infection was higher (48% vs. 26%). The main reasons for HCV non-treatment have changed: HCV treatment deemed questionable (44% vs. 53%), lack of liver biopsy (18% vs. 33%), physicians' conviction of poor patient compliance (20% vs. 30%). In both surveys, HCV treated patients were more often of European origin, had better control of HIV infection, and had a liver damage assessment more often. CONCLUSIONS: The care of HIV-HCV co-infected patients has changed significantly in "real life". These results underline the importance of continuing efforts to educate physicians and patients in order to increase the access of co-infected patients to HCV treatment.