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Patrice Cacoub - One of the best experts on this subject based on the ideXlab platform.
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Strategies to prevent persistent or relapsed mixed Cryoglobulinemia
Expert Opinion on Orphan Drugs, 2020Co-Authors: Gonçalo Boleto, David Saadoun, Patrice CacoubAbstract:Mixed Cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification.
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Cryoglobulinemia: An update in 2019.
Joint bone spine, 2019Co-Authors: Anne Claire Desbois, Patrice Cacoub, David SaadounAbstract:Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I Cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II Cryoglobulinemia), or only of polyclonal Igs (mixed type III Cryoglobulinemia). The manifestations of type I Cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed Cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I Cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed Cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin's lymphoma. The treatment depends mainly on the cause of the Cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated Cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I Cryoglobulinemia.
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hepatitis c virus infection mixed Cryoglobulinemia and kidney disease
American Journal of Kidney Diseases, 2013Co-Authors: Fabrizio Fabrizi, Emmanuelle Plaisier, D Saadoun, Paul Martin, Piergiorgio Messa, Patrice CacoubAbstract:Hepatitis C virus (HCV) may instigate mixed Cryoglobulinemia; the most significant accompanying kidney lesion is type I membranoproliferative glomerulonephritis, usually occurring in the context of type II mixed Cryoglobulinemia. Additionally, recent data support a link between HCV infection and proteinuria in population-based studies, raising the possibility that kidney diseases associated with HCV may be more common than previously thought. A number of strategies have been used to treat HCV-related glomerulonephritis, including antiviral agents, immunosuppressive therapies such as corticosteroids and cytotoxic agents, and plasma exchange. Limited but encouraging data about the utility of antiviral treatment in the setting of HCV-associated glomerulonephritis exist, with one pooled analysis noting a sustained viral response of 42%, albeit with significant heterogeneity. Immunosuppressive therapy may be most useful for cryoglobulinemic kidney disease, with individualized approaches considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis based on the level of proteinuria and kidney failure. Of note, rituximab, a chimeric monoclonal antibody that blocks CD20 receptors on B cells, has been reported to be effective for the treatment of mixed Cryoglobulinemia symptoms, including glomerulonephritis.
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treatment with rituximab in patients with mixed Cryoglobulinemia syndrome results of multicenter cohort study and review of the literature
Autoimmunity Reviews, 2011Co-Authors: Clodoveo Ferri, Patrice Cacoub, C Mazzaro, Dario Roccatello, Patrizia Scaini, Marco Sebastiani, A Tavoni, Anna Linda Zignego, S De VitaAbstract:Abstract Objective Mixed Cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of immune-complexes, mainly the cryoglobulins. B-lymphocyte expansion represents the underlying pathological alteration frequently triggered by hepatitis C virus (HCV) infection. The treatment of MCs syndrome is generally based on antiviral drugs and/or immunosuppressors, among which rituximab, an anti-CD20 monoclonal antibody, has been usefully employed for both cutaneous and visceral MCs organ involvement. This multicenter study retrospectively evaluated the effects of rituximab in a large series of patients with active MCs. The observed results were compared to those emerging from the updated review of the literature on this topic. Methods The study included 87 patients (male/female 19/68, mean age 62.3 ± 11.4SD years, mean disease duration 9 ± 6.2SD years, HCV infection in 92% of cases) with active cryoglobulinemic vasculitis evaluated before rituximab monotherapy and after 6-month follow-up by means of main clinico-serological parameters. A PubMed search up to May 31, 2011, was done to find published clinical studies, including case reports of MCs treated with rituximab. Results A significant clinical improvement was observed in a relevant percentage of cases, regardless the presence/absence of associated HCV infection; namely, complete/partial remission of pre-treatment active manifestations was observed in 74% of skin purpuric lesions, up to 87% of non-healing vasculitic leg ulcers, and 44% of the peripheral neuropathy, mainly paresthesias (patient's visual analogical scale from 62 ± 25 to 37 ± 27; p ≤ .0001). Moreover, cryoglobulinemic nephropathy, observed in 38 patients, significantly improved in 95% of cases (serum creatinine from 1.8 ± 1.1SD to 1.4 ± 0.8SD mg/dl, p ≤ .0001; 24-hour proteinuria from 2.2 ± 2.1SD to 0.9 ± 1.7SD g/24 h, p ≤ .0001), with complete remission in the 50%. Among 6 patients with complicating non-Hodgkin's B-cell lymphoma a complete or partial remission was observed in 5/6. A complete remission of abdominal vasculitis was also observed in one patient. These beneficial effects were mirrored by the improvement of cryoglobulinemic serological hallmarks, namely cryocrit and low complement C4, in half cases. The safety of rituximab was confirmed by the small number of side effects recorded during the 6-month follow-up. On the whole, the results of the present study are in keeping with those reported in 39 papers present in world literature, including a total of 279 MCs patients. Conclusions Rituximab may be regarded as useful and safe pathogenetic treatment of cryoglobulinemic vasculitis. The actual role of this drug should be definitely confirmed by randomized controlled trials, as well as its position in the therapeutical strategy, mainly with respect to antiviral treatment in HCV-associated MCs.
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Treatment of hepatitis C-associated mixed Cryoglobulinemia vasculitis.
Current Opinion in Rheumatology, 2008Co-Authors: David Saadoun, Aurelien Delluc, Jean Charles Piette, Patrice CacoubAbstract:PURPOSE OF REVIEW: Hepatitis C virus infection is the main cause of mixed Cryoglobulinemia vasculitis. The disease expression of mixed Cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, widespread vasculitis). Treatment of hepatitis C virus-mixed Cryoglobulinemia vasculitis may target either the viral trigger (hepatitis C virus) or the downstream B-cell arm of autoimmunity. This review focuses on recent advances in our understanding of the treatment of hepatitis C virus-mixed Cryoglobulinemia vasculitis. RECENT FINDINGS: Aggressive antiviral therapy with Peg-IFNalpha and ribavirin should be considered as induction therapy for hepatitis C virus-mixed Cryoglobulinemia vasculitis with mild to moderate disease severity and activity. In patients presenting with severe disease, an induction phase of immunosuppression is often necessary while awaiting the generally slow response to antiviral treatments. Combination therapy with rituximab and Peg-IFNalpha plus ribavirin appears logical as it may target both the viral trigger (hepatitis C virus) and cryoglobulin-producing B-cells. SUMMARY: Antiviral therapy and rituximab are the main therapeutic options in hepatitis C virus-mixed Cryoglobulinemia vasculitis. Further studies are needed to better define the therapeutic strategy.
Clodoveo Ferri - One of the best experts on this subject based on the ideXlab platform.
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systemic sclerosis and Cryoglobulinemia our experience with overlapping syndrome of scleroderma and severe cryoglobulinemic vasculitis and review of the literature
Autoimmunity Reviews, 2013Co-Authors: Dilia Giuggioli, Andreina Teresa Manfredi, Michele Colaci, Carlo Umberto Manzini, Alessandro Antonelli, Clodoveo FerriAbstract:Abstract Objective Systemic sclerosis (SSc) is an immune-mediated disorder characterized by multiple organ fibrotic alterations and diffuse microangiopathy. The SSc can be associated with other connective tissue diseases and less frequently with systemic vasculitides, including cryoglobulinemic vasculitis (CV). The aim of the present study was to investigate the prevalence of CV in a large series of SSc patients. Methods The presence of serum cryoglobulins was detected in 246 SSc patients (24 M and 222 F, age 61 ± 13.5 SD years, disease duration 9.3 ± 6.7 SD years); the observed clinico-serological findings, in particular the presence of SSc–CV overlapping syndrome, were carefully analyzed and compared with previous data reported in the literature. Results The presence of circulating cryoglobulins was found in 7/246 (2.8%) of SSc patients; namely, 2 subjects only trace amounts of cryoglobulins, while 5 (2%) showed mixed Cryoglobulinemia (type II, IgG-IgMk), low C4, rheumatoid factor seropositivity, and hepatitis C virus infection. Among SSc patients with serum mixed cryoglobulins, 4 (1.6%) developed a clinically overt CV, while the other one was totally asymptomatic with regard to typical vasculitic manifestations. Patients with SSc–CV overlapping syndrome had limited cutaneous SSc with serum anticentromere antibodies, pulmonary hypertension, clinico-serological features of HCV-related CV, and non-healing skin ulcers of the lower limbs. In all cases, the diagnosis of SSc preceded the clinical onset of CV, from 3 to 17 years. The treatment with rituximab was useful on skin ulcers of lower limb in 2/3 patients; however, the overall clinical outcome of the four SSc–CV patients was unusually severe: one with very severe skin ulcers complicated by gangrene required bilateral through-the knee amputation, the other three subjects died because of severe heart failure, and in two cases because of untreatable pulmonary hypertension. In the literature, the prevalence of mixed Cryoglobulinemia in scleroderma patients is quite rare (range 0.3–2%); while, the association of SSc with clinically overt CV is only anecdotally described, always in the absence of HCV infection. Conclusion The SSc–CV overlapping syndrome described here is characterized by markedly severe vascular manifestations responsible for very poor prognosis; these peculiar clinical manifestations suggest a synergic activity of typical scleroderma microangiopathy and cryoglobulinemic vasculitis.
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treatment with rituximab in patients with mixed Cryoglobulinemia syndrome results of multicenter cohort study and review of the literature
Autoimmunity Reviews, 2011Co-Authors: Clodoveo Ferri, Patrice Cacoub, C Mazzaro, Dario Roccatello, Patrizia Scaini, Marco Sebastiani, A Tavoni, Anna Linda Zignego, S De VitaAbstract:Abstract Objective Mixed Cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of immune-complexes, mainly the cryoglobulins. B-lymphocyte expansion represents the underlying pathological alteration frequently triggered by hepatitis C virus (HCV) infection. The treatment of MCs syndrome is generally based on antiviral drugs and/or immunosuppressors, among which rituximab, an anti-CD20 monoclonal antibody, has been usefully employed for both cutaneous and visceral MCs organ involvement. This multicenter study retrospectively evaluated the effects of rituximab in a large series of patients with active MCs. The observed results were compared to those emerging from the updated review of the literature on this topic. Methods The study included 87 patients (male/female 19/68, mean age 62.3 ± 11.4SD years, mean disease duration 9 ± 6.2SD years, HCV infection in 92% of cases) with active cryoglobulinemic vasculitis evaluated before rituximab monotherapy and after 6-month follow-up by means of main clinico-serological parameters. A PubMed search up to May 31, 2011, was done to find published clinical studies, including case reports of MCs treated with rituximab. Results A significant clinical improvement was observed in a relevant percentage of cases, regardless the presence/absence of associated HCV infection; namely, complete/partial remission of pre-treatment active manifestations was observed in 74% of skin purpuric lesions, up to 87% of non-healing vasculitic leg ulcers, and 44% of the peripheral neuropathy, mainly paresthesias (patient's visual analogical scale from 62 ± 25 to 37 ± 27; p ≤ .0001). Moreover, cryoglobulinemic nephropathy, observed in 38 patients, significantly improved in 95% of cases (serum creatinine from 1.8 ± 1.1SD to 1.4 ± 0.8SD mg/dl, p ≤ .0001; 24-hour proteinuria from 2.2 ± 2.1SD to 0.9 ± 1.7SD g/24 h, p ≤ .0001), with complete remission in the 50%. Among 6 patients with complicating non-Hodgkin's B-cell lymphoma a complete or partial remission was observed in 5/6. A complete remission of abdominal vasculitis was also observed in one patient. These beneficial effects were mirrored by the improvement of cryoglobulinemic serological hallmarks, namely cryocrit and low complement C4, in half cases. The safety of rituximab was confirmed by the small number of side effects recorded during the 6-month follow-up. On the whole, the results of the present study are in keeping with those reported in 39 papers present in world literature, including a total of 279 MCs patients. Conclusions Rituximab may be regarded as useful and safe pathogenetic treatment of cryoglobulinemic vasculitis. The actual role of this drug should be definitely confirmed by randomized controlled trials, as well as its position in the therapeutical strategy, mainly with respect to antiviral treatment in HCV-associated MCs.
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prevalence of bcl 2 rearrangement in patients with hepatitis c virus related mixed Cryoglobulinemia with or without b cell lymphomas
Annals of Internal Medicine, 2002Co-Authors: Anna Linda Zignego, Clodoveo Ferri, Francesca Giannelli, C Giannini, P Caini, Monica Monti, M E Marrocchi, Elena Di Pietro, Giorgio La Villa, Giacomo LaffiAbstract:Patients with chronic hepatitis C and mixed Cryoglobulinemia had increased frequency of bcl-2 rearrangement. The frequency was greatest in patients with type II mixed Cryoglobulinemia. The high rat...
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Antibodies against hepatitis C virus in mixed Cryoglobulinemia patients.
Infection, 1991Co-Authors: Clodoveo Ferri, F. Greco, Giovanni Longombardo, P Palla, A Moretti, E Marzo, Pv Fosella, Giampiero Pasero, Stefano BombardieriAbstract:The prevalence of antibodies against hepatitis C virus (anti-HCV) in an unselected series of 45 mixed Cryoglobulinemia patients was assessed by an enzyme linked immunosorbent assay (Chiron ELISA HCV, Second Generation). The anti-HCV specificity was evaluated by a recombinant based immunoblot assay (Chiron RIBA HCV, Second Generation Assay). HBV-related markers and HIVAb were detected in the same samples. The prevalence of anti-HCV observed in mixed Cryoglobulinemia was compared with 80 patients with other immunological systemic diseases. Anti-HCV were found in 91% of mixed Cryoglobulinemia patients, and confirmed by RIBA in all cases; on the other hand, anti-HCV were practically absent in other control diseases. HBV markers were recorded in 49% of mixed Cryoglobulinemia subjects; while HIVAb were constantly absent. These data give us new insights into the etiopathogenesis of mixed Cryoglobulinemia.
David Saadoun - One of the best experts on this subject based on the ideXlab platform.
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Strategies to prevent persistent or relapsed mixed Cryoglobulinemia
Expert Opinion on Orphan Drugs, 2020Co-Authors: Gonçalo Boleto, David Saadoun, Patrice CacoubAbstract:Mixed Cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification.
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Cryoglobulinemia: An update in 2019.
Joint bone spine, 2019Co-Authors: Anne Claire Desbois, Patrice Cacoub, David SaadounAbstract:Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I Cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II Cryoglobulinemia), or only of polyclonal Igs (mixed type III Cryoglobulinemia). The manifestations of type I Cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed Cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I Cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed Cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin's lymphoma. The treatment depends mainly on the cause of the Cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated Cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I Cryoglobulinemia.
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Treatment of hepatitis C-associated mixed Cryoglobulinemia vasculitis.
Current Opinion in Rheumatology, 2008Co-Authors: David Saadoun, Aurelien Delluc, Jean Charles Piette, Patrice CacoubAbstract:PURPOSE OF REVIEW: Hepatitis C virus infection is the main cause of mixed Cryoglobulinemia vasculitis. The disease expression of mixed Cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, widespread vasculitis). Treatment of hepatitis C virus-mixed Cryoglobulinemia vasculitis may target either the viral trigger (hepatitis C virus) or the downstream B-cell arm of autoimmunity. This review focuses on recent advances in our understanding of the treatment of hepatitis C virus-mixed Cryoglobulinemia vasculitis. RECENT FINDINGS: Aggressive antiviral therapy with Peg-IFNalpha and ribavirin should be considered as induction therapy for hepatitis C virus-mixed Cryoglobulinemia vasculitis with mild to moderate disease severity and activity. In patients presenting with severe disease, an induction phase of immunosuppression is often necessary while awaiting the generally slow response to antiviral treatments. Combination therapy with rituximab and Peg-IFNalpha plus ribavirin appears logical as it may target both the viral trigger (hepatitis C virus) and cryoglobulin-producing B-cells. SUMMARY: Antiviral therapy and rituximab are the main therapeutic options in hepatitis C virus-mixed Cryoglobulinemia vasculitis. Further studies are needed to better define the therapeutic strategy.
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Treatment of hepatitis C-associated mixed Cryoglobulinemia vasculitis.
Current opinion in rheumatology, 2008Co-Authors: David Saadoun, Aurelien Delluc, J C Piette, Patrice CacoubAbstract:Purpose of reviewHepatitis C virus infection is the main cause of mixed Cryoglobulinemia vasculitis. The disease expression of mixed Cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, wid
J C Piette - One of the best experts on this subject based on the ideXlab platform.
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Treatment of hepatitis C-associated mixed Cryoglobulinemia vasculitis.
Current opinion in rheumatology, 2008Co-Authors: David Saadoun, Aurelien Delluc, J C Piette, Patrice CacoubAbstract:Purpose of reviewHepatitis C virus infection is the main cause of mixed Cryoglobulinemia vasculitis. The disease expression of mixed Cryoglobulinemia vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, wid
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Transfusion-associated TT virus co-infection in patients with hepatitis C virus is associated with type II mixed Cryoglobulinemia but not with B-cell non-Hodgkin lymphoma
Clinical Microbiology and Infection, 2003Co-Authors: P. Cacoub, J C Piette, E. Rosenthal, V. Gerolami, P. Hausfater, P. Ghillani, Y. Sterkers, V. Thibault, H. Khiri, P. HalfonAbstract:OBJECTIVE: To assess the prevalence of TT virus (TMV) infection in a series of patients with chronic hepatitis C virus (HCV) infection, with or without benign (mixed Cryoglobulinemia) or malignant (B-cell non-Hodgkin lymphoma (B-NHL)) lymphoproliferative disease. METHODS: Sixty-six HCV patients were studied, including patients with mixed Cryoglobulinemia (n=30), B-NHL (n=15), and no mixed Cryoglobulinemia or B-NHL (n=21). All HCV patients had increased transaminase levels and were HCV RNA positive. Patients were considered to have mixed Cryoglobulinemia if two successive determinations of their serum cryoglobulin level were above 0.05 g/L. Mixed Cryoglobulinemia-negative patients never had mixed cryoglobulins in their serum on multiple determinations. Subjects without HCV infection included 79 patients with histologically proven B-NHL, and 50 healthy blood donors. Serum samples were analyzed for TTV DNA by nested polymerase chain reaction, with two couples of primers in different regions of the genome, in two independent laboratories. RESULTS: In the group of HCV-positive patients, TTV DNA was found in one of 15 (6.7%) patients with B-NHL, and in nine of 51 (17.6%, P = 0.43) of those without B-NHL. Among HCV-positive patients without B-NHL, TTV DNA was more frequently found in those with type II mixed Cryoglobulinemia vasculitis than in those without it (six of 16 (37.5%) versus two of 21 (9.5%), P = 0.05). In subjects without HCV infection, TTV DNA was present in 10 of 79 (12.7%) patients with B-NHL and in seven of 50 (14.0%, P = 0.82) blood donors. CONCLUSION: In patients chronically infected with HCV, TTV co-infection: (1) is not associated with the presence of B-NHL; and (2) is more frequently found in patients presenting a type II mixed Cryoglobulinemia vasculitis.
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Cryoglobulinemia in chronic liver diseases role of hepatitis c virus and liver damage
Gastroenterology, 1994Co-Authors: F Lunel, Patrice Cacoub, Lucile Musset, Lionel Frangeul, Pascale Cresta, Michele Perrin, P Grippon, C Hoang, J C Piette, J M HurauxAbstract:Abstract Background/Aims: Mixed Cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of Cryoglobulinemia is investigated in this study. Methods: The prevalence of Cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. Results: The prevalence of mixed Cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with Cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. Conclusions: These findings suggest that HCV is a major cause of Cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.
Anna Linda Zignego - One of the best experts on this subject based on the ideXlab platform.
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treatment with rituximab in patients with mixed Cryoglobulinemia syndrome results of multicenter cohort study and review of the literature
Autoimmunity Reviews, 2011Co-Authors: Clodoveo Ferri, Patrice Cacoub, C Mazzaro, Dario Roccatello, Patrizia Scaini, Marco Sebastiani, A Tavoni, Anna Linda Zignego, S De VitaAbstract:Abstract Objective Mixed Cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of immune-complexes, mainly the cryoglobulins. B-lymphocyte expansion represents the underlying pathological alteration frequently triggered by hepatitis C virus (HCV) infection. The treatment of MCs syndrome is generally based on antiviral drugs and/or immunosuppressors, among which rituximab, an anti-CD20 monoclonal antibody, has been usefully employed for both cutaneous and visceral MCs organ involvement. This multicenter study retrospectively evaluated the effects of rituximab in a large series of patients with active MCs. The observed results were compared to those emerging from the updated review of the literature on this topic. Methods The study included 87 patients (male/female 19/68, mean age 62.3 ± 11.4SD years, mean disease duration 9 ± 6.2SD years, HCV infection in 92% of cases) with active cryoglobulinemic vasculitis evaluated before rituximab monotherapy and after 6-month follow-up by means of main clinico-serological parameters. A PubMed search up to May 31, 2011, was done to find published clinical studies, including case reports of MCs treated with rituximab. Results A significant clinical improvement was observed in a relevant percentage of cases, regardless the presence/absence of associated HCV infection; namely, complete/partial remission of pre-treatment active manifestations was observed in 74% of skin purpuric lesions, up to 87% of non-healing vasculitic leg ulcers, and 44% of the peripheral neuropathy, mainly paresthesias (patient's visual analogical scale from 62 ± 25 to 37 ± 27; p ≤ .0001). Moreover, cryoglobulinemic nephropathy, observed in 38 patients, significantly improved in 95% of cases (serum creatinine from 1.8 ± 1.1SD to 1.4 ± 0.8SD mg/dl, p ≤ .0001; 24-hour proteinuria from 2.2 ± 2.1SD to 0.9 ± 1.7SD g/24 h, p ≤ .0001), with complete remission in the 50%. Among 6 patients with complicating non-Hodgkin's B-cell lymphoma a complete or partial remission was observed in 5/6. A complete remission of abdominal vasculitis was also observed in one patient. These beneficial effects were mirrored by the improvement of cryoglobulinemic serological hallmarks, namely cryocrit and low complement C4, in half cases. The safety of rituximab was confirmed by the small number of side effects recorded during the 6-month follow-up. On the whole, the results of the present study are in keeping with those reported in 39 papers present in world literature, including a total of 279 MCs patients. Conclusions Rituximab may be regarded as useful and safe pathogenetic treatment of cryoglobulinemic vasculitis. The actual role of this drug should be definitely confirmed by randomized controlled trials, as well as its position in the therapeutical strategy, mainly with respect to antiviral treatment in HCV-associated MCs.
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prevalence of bcl 2 rearrangement in patients with hepatitis c virus related mixed Cryoglobulinemia with or without b cell lymphomas
Annals of Internal Medicine, 2002Co-Authors: Anna Linda Zignego, Clodoveo Ferri, Francesca Giannelli, C Giannini, P Caini, Monica Monti, M E Marrocchi, Elena Di Pietro, Giorgio La Villa, Giacomo LaffiAbstract:Patients with chronic hepatitis C and mixed Cryoglobulinemia had increased frequency of bcl-2 rearrangement. The frequency was greatest in patients with type II mixed Cryoglobulinemia. The high rat...