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P Cacoub

Publications and source records attributed to P Cacoub.

At least 55 records · Page 3Linked to original sources
PubMed2002

Plasma exchange and interferon-alpha pharmacokinetics in patients with hepatitis C virus-associated systemic vasculitis.

UNLABELLED: Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. PATIENTS AND METHODS: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. RESULTS: Without PE, IFN C(max )(range: 100-750 IU/ml) was obtained 3-6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-alpha area under the curve decreased from 3,005 IU x h/ml (1,563-4,614) on days without PE to 2,142 IU x h/ml (973-4,123) on day with PE. CONCLUSIONS: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-alpha and PE therapy schedule have to be further studied to optimize its biological activity.

Aged↗
PubMed2002

[Neurological manifestations in cryoglobulinemia].

Cryoglobulins are immunoglobulins that persist in the serum, precipitate at cold temperature and resolubilize when rewarmed. Type I is often associated with hematological disorders. Type II and III are mixed cryoglobulins, composed of different immunoglobulins with a monoclonal component in type II and only polyclonal immunoglobulins in type III. Mixed cryoglobulins are associated with connective tissues or infectious diseases. Hepatitis C virus is involved in most of previously called "essential" mixed cryoglobulinemia. Dermatological, rhumatological, and nephrological manifestations are the most frequent, and neurological complications are found in 20 percent of cases. However, in mixed cryoglobulinemia with low cryoglobulins level, neurological signs may reveal the disease. Ischemic central nervous system complications are rare, but sensory, axonal, peripheral neuropathies or sensory and motor multiple mononeuropathies are more frequent. Prognostic and treatment depend on association with hepatitis C, and presence of vasculitis lesions in the nerve biopsy.

Central Nervous System Diseases↗
PubMed2001

Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997.

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.

AIDS-Related Opportunistic Infections↗
PubMed2001

A new type of acquired C1 inhibitor deficiency associated with systemic lupus erythematosus.

Acquired C1 inhibitor (C1-INH) deficiency with consequent angioedema is a rare condition that may indicate an underlying lymphoproliferative disorder. The defect is caused by increased catabolism, which is often associated with the presence of serum autoantibodies to C1-INH. The present report describes 3 patients with systemic lupus erythematosus who developed typical symptoms of acquired angioedema, characterized by recurrent swelling of subcutaneous and mucous tissues. The 3 patients demonstrated a major classical pathway-mediated complement consumption, with very low levels of C3 antigen and decreased levels of C1-INH antigen. Neither antibodies to C1-INH nor associated lymphoproliferative disease was found. No patient had clinical and biologic signs of lupus activity at the time the angioedema occurred. All patients were treated with steroids and exhibited a good response, without relapse of angioedema and with normalization of plasma levels of C1-INH. In lupus patients who present with an angioedema syndrome, acquired or hereditary angioedema must be sought by examining parameters of the classical pathway and levels of C1-INH. Our observations suggest the existence of a new form of acquired C1-INH deficiency associated with a major classical pathway-mediated complement consumption and systemic autoimmunity.

Adolescent↗
PubMed2001

Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia.

OBJECTIVE: Circumstances predisposing hepatitis C virus (HCV)-infected patients to develop mixed cryoglobulinemia (MC), which may manifest as a small-vessel systemic vasculitis (MC vasculitis), remain unclear. Previous studies have failed to demonstrate a clear role of either viral factors (genotype, viral load) or host factors (lymphocytes or immunoglobulin subsets). This study was undertaken to examine a possible role of HLA class II alleles in HCV-associated MC. METHODS: One hundred fifty-eight HCV-infected patients, of whom 76 had MC (56 with type II MC and 20 with type III MC) and 82 did not have MC, were studied prospectively. MC vasculitis was noted in 35 HCV-infected patients with type II IgMkappa-containing cryoglobulins. HLA-DRB1 and HLA-DQB1 polymorphism was analyzed by hybridization using allele-specific oligonucleotides, after gene amplification. The odds ratio (OR) was calculated with Woolf's method. Then, using multivariate analysis, demographic, biologic, immunologic, virologic, and liver histologic factors associated with the presence of MC and MC vasculitis were investigated. RESULTS: HLA-DR11 was significantly more frequent in patients with type II MC than in those without MC (41.1% versus 17.1%; OR 3.4, corrected P [Pcorr] = 0.017), regardless of the presence of vasculitis accompanying the MC (37.1% of those with MC vasculitis, 34.1% of those with MC but no vasculitis). HLA-DR7 was less frequent in HCV-infected patients with MC than in those without MC (13.2% versus 30.5%; OR 0.34, P = 0.012, Pcorr not significant), with a particularly lower frequency in those with type II MC and those with MC vasculitis (12.5% and 8.6%, respectively). There was no significant difference in HLA-DQB1 distribution between the different patient groups. By univariate and multivariate analysis, HLA-DR11 was the only positive predictive factor, besides female sex and advanced age, for the presence of MC and HCV-associated MC vasculitis (OR 2.58). CONCLUSION: Our results indicate that the presence of the DR11 phenotype is associated with a significantly increased risk for the development of type II MC in patients with chronic HCV infection. In contrast, HLA-DR7 appears to protect against the production of type II MC. These results suggest that the host's immune response genes may play a role in the pathogenesis of HCV-associated MC.

Adult↗
PubMed2001

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 Waldenström'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.

Adolescent↗
PubMed2001

Neurological complications of primary Sjögren's syndrome.

OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.

Adult↗
PubMed2001

Postvaccine vasculitis: a report of three cases.

INTRODUCTION: Vaccines may be responsible for adverse effects, mainly local fugitive and benign reactions. However, few cases of systemic vasculitis have been described. We report three new cases, suggesting the responsibility of vaccination in starting or reactivating systemic vasculitis. EXEGESIS: We report two cases in a 64- and a 68-year-old woman with polymyalgia rheumatica and temporal arteritis after influenza and tetanus vaccination respectively, and one case in a 30-year-old man with periarteritis nodosa after hepatitis B vaccination. CONCLUSION: Knowledge of such complications deserve to be expanded in order to: 1) avoid re-immunisations which are likely to result in more serious consequences; 2) avoid aggravation or reactivation of a vasculitis; and 3) control serology before hepatitis B vaccination in all persons at risk of HBV infection.

Adult↗
PubMed2001

[Peripheral neuropathy and hepatitis C virus infection: more than cryoglobulinemia].

PURPOSE: To study characteristics of peripheral neuropathies associated with hepatitis C virus infection. METHODS: A study of two groups of four patients with peripheral neuropathy and infected with hepatitis C virus, and a literature review. RESULTS: We observed four cases of peripheral neuropathy in patients with hepatitis C virus infection with persistent negativity of mixed cryoglobulinemia, and with no purpura, rheumatoid factor, or low C4 level. Neuropathy improved with treatment in three patients between 8 and 28 months after treatment was begun. We report four other observations of peripheral neuropathy with mixed cryoglobulinemia. Worsening of peripheral neuropathy was observed 2 to 13 weeks after initiation of interferon alpha despite improvement of hepatic parameters. After stopping interferon, peripheral neuropathy worsened (one case), stabilized (one case), or improved (two cases). DISCUSSION: In patients infected with hepatitis C virus, peripheral neuropathy can be due to mixed cryoglobulinemia, periarteritis nodosa, and perhaps hepatitis C virus itself as suggested by our first observations. Low doses of interferon alpha may worsen peripheral neuropathy in patients with mixed cryoglobulinemia, as suggested in our later observations.

Adult↗
PubMed2001

Effect of 51p1-related gene copy number (V1-69 locus) on production of hepatitis C-associated cryoglobulins.

Monoclonal IgM in type II mixed cryoglobulins (MC) preferentially use 51p1-related immunoglobulin VH genes. In normal preimmune B lymphocytes, 51p1-related gene expression is proportional to the germ-line gene dosage, which can be 0-4. To determine whether 51p1-related gene dosage influences the occurrence of type II MC or the VH gene bias in cryoglobulin IgM, we studied 47 patients chronically infected with hepatitis C virus (HCV), 24 MC+, 23 MC-. By Western analysis, 11 cryoprecipitate IgM (46%) were detected by G6 (a marker for 51p1-related gene products), eight (33%) by Staphylococcal Protein A (a VH3 family marker), and five (21%) by neither, indicating a 23-fold bias favouring 51p1-related genes. All 11 MC+, G6+ patients possessed > or = 1 copy of a 51p1-related gene; nine of the 36 others had none. The mean copy number of 51p1-related genes was greater in MC+ than MC- patients, and in MC+, G6+ patients versus the 36 others (P < 0.04), but significant differences were not seen in analyses restricted to patients with > or = 1 copy of a 51p1-related gene. We conclude that when a 51p1-related gene is present, a strong bias favours G6+ IgM in HCV-associated type II MC, but this bias is not greatly increased by a high dosage of 51p1-related genes. Furthermore, patients lacking 51p1-related genes also produce MC, but with G6- IgM.

Adolescent↗
PubMed2001

Hepatitis C virus infection with peripheral neuropathy is not always associated with cryoglobulinaemia.

OBJECTIVES: To describe cases of peripheral neuropathy associated with chronic hepatitis C virus infection without mixed cryoglobulinaemia. METHODS: Four cases of peripheral neuropathy associated with chronic hepatitis C virus infection with persistent negativity of mixed cryoglobulinaemia were found. RESULTS: All patients had small increases of transaminase levels and a positive viraemia. Liver biopsy showed chronic active hepatitis in all but one case (Knodell 4-9, Metavir A0F0-A3F3). Neuromuscular biopsy showed axonal neuropathy associated with lymphoid infiltrates around small vessels in two cases. Rheumatoid factor was always negative and C4 complement level was always normal. In three patients, neuropathy improved with interferon alpha, interferon alpha + ursodesoxycholic acid, or steroids + plasma exchange. CONCLUSION: Peripheral neuropathy may be associated with hepatitis C virus infection without mixed cryoglobulinaemia.

Adult↗
PubMed2001

Systemic vasculitis in patients with hepatitis C.

OBJECTIVE: To analyze the main characteristics of patients infected with hepatitis C virus (HCV) presenting with different types of vasculitis syndrome. METHODS: We retrospectively compared 2 groups of patients with HCV presenting with systemic vasculitis: 10 with biopsy proven polyarteritis nodosa-type systemic vasculitis (PAN, Group 1) and 7 with mixed cryoglobulinemia syndrome (MC, Group 2). RESULTS: Patients of Group 1 presented with different features than Group 2: life threatening systemic vasculitis (10 vs 0; p < 0.01), severe multifocal sensorimotor mononeuropathies versus distal moderate sensory polyneuropathies, malignant hypertension (5 vs 0; p = 0.04), cerebral angiitis (2 vs 0), ischemic abdominal pain (2 vs 0), kidney and liver microaneurisms (2 vs 0), increased erythrocyte sedimentation rate and C-reactive protein (7 vs 0; p < 0.01), renal insufficiency (5 vs 0; p = 0.04), HCV genotype 1b (3 vs 6; p = 0.06), and lower activity of chronic hepatitis (p = 0.02). Neuromuscular biopsies showed lesions of vasculitis in all patients, but the type of vasculitis was different in Group 1 compared to Group 2: medium size artery involvement (7 vs 0; p < 0.01), necrotizing vasculitis (10 vs 0; p < 0.01), and mononuclear cell infiltrate in perivascular areas (0 vs 7; p < 0.01). Using prednisone, plasma exchanges, and interferon-alpha, complete recovery was obtained in all PAN-type patients except one. In Group 2 patients, interferon-alpha did not have any effect on the peripheral neuropathy. CONCLUSION: HCV infection may be associated with different types of systemic vasculitis, i.e., polyarteritis nodosa or mixed cryoglobulinemia. Because of differences in clinical and pathological features and therapeutic strategy, PAN-type vasculitis should be distinguished from MC-type vasculitis in HCV patients.

Adult↗
PubMed2001

Autoantibodies to receptor induced neoepitopes of fibrinolytic proteins in rheumatic and vascular diseases.

OBJECTIVE: Abnormal plasminogen activation has been implicated in vascular and rheumatic diseases. The development of an autoimmune response to neoepitopes of plasminogen and its activator (tissue-type plasminogen activator, t-PA) was explored in sera from patients with rheumatoid arthritis (RA, n = 30), Behcet's disease (n = 20), primary antiphospholipid syndrome (APS, n = 23), and idiopathic arterial (n = 33) or venous thrombosis (n = 16). METHODS: Sera diluted 1/50 were incubated with either plasminogen or t-PA bound to their natural receptors (immobilized fibrin or monocytic cells), and bound immunoglobulins were detected using a sheep peroxidase labeled anti-human Fab IgG. Controls included plates coated with fibrin or cells alone or plasminogen passively adsorbed to the plastic. Sera were considered positive when the absorbance at 405/490 nm was above the mean + 2 SD of normal sera. RESULTS: Reactivity of sera against plasminogen bound to cells (28%) or to fibrin (22%) was a predominant feature in patients with RA compared with other patient groups and controls. However, some patients with primary APS had reactivity against cell and fibrin bound plasminogen (9 and 13%, respectively). Autoantibodies against fibrin bound t-PA were detected in only 8% of patients with arterial or venous thrombosis. CONCLUSION: Conformational changes induced by molecular assembly of plasminogen on cell or fibrin surfaces result in the expression of neoepitopes recognized by autoantibodies. These autoantibodies could be markers of the proteolytic events associated with plasminogen activation in autoimmune diseases.

Adult↗
PubMed2001

[Intramedullary spinal cord sarcoidosis. Case report and review of the literature].

Sarcoidosis is a multisystemic granulomatosis disease of unknown etiology which commonly involves hilary nodes and lungs. Involvement of the nervous system represents 5 to 15% of the cases. We report on a rare case of cervicothoracic spinal cord sarcoidosis in an African man and review the literature on the subject. His only symptoms were those of a subacute myelopathy. On MR-imaging, coexistence of abnormal signal of cervicothoracic spinal cord with mediastinal lymph nodes was suggestive of sarcoidosis, which was confirmed by bronchial biopsies making unnecessary biopsies of the spinal cord lesion. Under corticotherapy both symptoms and radiological abnormalities rapidly regressed. We emphasize the rarity of sarcoidosis exclusively revealed by a myelopathy. We stress the importance of searching other localizations which are easier and safer to biopsy than the spinal cord lesion itself and illustrate the MR appearances of the lesion which are suggestive, however not specific of the disease.

Adult↗