Direct-acting antiviral agents for hepatitis C virus-mixed cryoglobulinaemia: dissociated virological and haematological responses.

The hepatitis C virus-positive (HCV+) mixed cryoglobulinaemia (MC) is associated with haematological alterations such as monoclonal B-cell lymphocytosis or non-Hodgkin lymphomas (NHLs). Antiviral therapy for MC, based on interferon and ribavirin, has been shown to be able to eliminate the viral replication as well as the B-cell monoclonal alterations. Many studies have reported the efficacy of direct-acting antivirals (DAAs) in the treatment of HCV+ MC. However, some authors noticed the persistence of haematological diseases despite HCV eradication. To verify the effects of DAAs on B-cell proliferation, we evaluated 67 patients with HCV+ MC. Six patients had an overt NHL and 30% had monoclonal B-lymphocytosis. In 20% of the patients, the mutation L265P of the myeloid differentiation factor 88 (MYD88) gene was detected in peripheral blood. All patients had negative HCV viraemia at week 12; one had a breakthrough, while two cases relapsed. A complete clinical response of vasculitis was seen in 60% of the patients. Among the six patients with NHL, one showed a complete response, whereas in the others there were no changes in the number and size of the nodes. Among the patients carrying a clonal population in peripheral blood, only 22% became negative. These data indicate that DAAs are not able to eliminate the clonal alterations induced by HCV in a large proportion of cases.

Acute renal failure secondary to severe type I cryoglobulinemia following rituximab therapy for Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is rare lymphoproliferative disorder characterized by the presence of a monoclonal IgM paraproteinemia. Cryoglobulinemia is a common sequela of Waldenström's macroglobulinemia present in 8-18% of the patients. Cryoglobulinemia has also been described as occurring after treatment with rituximab. In the previous report, the cryoglobulinemia was a transient phenomenon and did not carry any adverse effect. We present a case of an 80-year-old male with Waldenström's macroglobulinemia in whom the rituximab-induced cryoglobulinemia resulted in acute renal failure and a vasculitic rash. Cryoglobulins level reached a peak of 63%. The patient was successfully treated with plasmapheresis, chlorambucil and prednisone, with near-complete recovery of renal function. As this case illustrates, the rituximab-induced cryoglobulin is not always benign. Pre- and post-treatment monitoring of the cryoglobulin level is advised in these patients.

The use of monoclonal antibody (rituximab) in the treatment of type II mixed cryoglobulinemia.

Anti-CD20 monoclonal antibody has been successfully used to treat several self-immune diseases. The authors report the case of a 71 year-old female patient under the use of pegylated form of interferon á associated with ribavirin for the treatment of hepatitis C, who, after concluding the therapeutic program - negative Polymerase Chain Reaction (PCR) - developed a severe cutaneous vasculitis, receiving the diagnostic of type II mixed cryoglobulinemia. Four sessions of plasmapheresis were prescribed along the period of 11 days, with no result. The choice made was to administer anti-CD 20 monoclonal antibody (rituximab), 375 mg/m(2), per week, during four consecutive weeks. One could observe fast recovery from the purpura, as well as total remission of urticaria.

Case of mononeuritis multiplex onset with rituximab therapy for Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic disorder with associated monoclonal gammopathy. A wide variety of neuropathies can be associated with WM, but most commonly it is a mild length-dependent sensory neuropathy of unclear etiology. Rituximab is a monoclonal antibody which suppresses mature B-cell populations. It has increasingly been used in wide applications including WM, especially in those cases with severe neuropathy. The highlighted case provides an example of rituximab treatment complication in a WM patient with mild sensory neuropathy that evolved to multiple mononeuropathies with features of systemic vasculitis and unusual conversion of type I to type II cryoglobulinemia.

[A case of peripheral facial nerve palsy with cryoglobulinemia and chronic thyroiditis occurring during interferon plus ribavirin therapy for chronic hepatitis C].

A 42-year-old woman with chronic hepatitis C has visited our hospital since October 2003. Liver biopsy revealed chronic hepatitis (A1/F1) . Therapy was initiated with interferon (IFN) alpha-2b and ribavirin in February 2004. Two months later, the patient developed left facial weakness. Laboratory findings showed cryoglobulinemia and abnormal thyroid function without any evidence of other viral infections. Idiopathic peripheral facial nerve palsy was diagnosed. IFN was discontinued at week 9 of therapy, but she obtained sustained virological response and her symptoms resolved at 6 month after the withdrawal.

Symptomatic and virological response to antiviral therapy in hepatitis C associated with extrahepatic complications of cryoglobulimia.

Mixed cryoglobulins are detected in 50% of patients with hepatitis C; fortunately, few have vasculitis affecting skin, peripheral nerves, kidneys, and synovia. This study was designed to identify the natural history of symptomatic cryoglobulinemia and evaluate the response to antiviral therapy. Patients with hepatitis C complicated by symptomatic cryoglobulinemia were assessed for their disease manifestations and response to antiviral therapy. Of 83 patients identified, 56 patients with a minimum of 12 months follow-up were reviewed. Manifestations included dermatologic (75%), rheumatologic (57%), neurologic (34%), and renal (proteinuria 25%). Antiviral therapy was given to 38, of whom 9 were retreated for symptomatic and/or virological nonresponse. Antiviral therapy included interferon monotherapy (n= 8), pegylated-interferon monotherapy (n= 5), consensus-interferon (n= 2), interferon + ribavirin (n= 18), and pegylated-interferon + ribavirin (n= 14). Treatment provided sustained symptomatic response in 31 (82%) and virological response in 16 (42%) patients. Symptomatic cryoglobulinemia responds well to antiviral therapy, even when virological response is not achieved.

The use of monoclonal antibody (Rituximab) in the treatment of type II mixed cryoglobulinemia

Anti-CD20 monoclonal antibody has been successfully used to treat several self-immune diseases. The authors report the case of a 71 year-old female patient under the use of pegylated form of interferon á associated with ribavirin for the treatment of hepatitis C, who, after concluding the therapeutic program - negative Polymerase Chain Reaction (PCR) - developed a severe cutaneous vasculitis, receiving the diagnostic of type II mixed cryoglobulinemia. Four sessions of plasmapheresis were prescribed along the period of 11 days, with no result. The choice made was to administer anti-CD 20 monoclonal antibody (rituximab), 375 mg/m², per week, during four consecutive weeks. One could observe fast recovery from the purpura, as well as total remission of urticaria.

[Treatment of paraproteinemia]. / Leczenie paraproteinemii.

Contemporary view on diagnosis and treatment of paraproteinemia is presented dealing particularly with nephrological implications. Treatment of multiple myeloma including new drugs is presented in details. Treatment of cryofibrinogenemia and amyloidosis are also reviewed.

Mixed cryoglobulinemia secondary to interferon therapy for hepatitis C: case report & review of the literature.

Mixed cryoglobulinemia is a systemic vasculitis associated with hepatitis C infection. We present a case of mixed cryoglobulinemia induced by interferon-alpha therapy for hepatitis C infection and review previous cases in which cryoglobulinemic symptom exacerbations were caused by interferon-alpha.

[Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years]. / Purpura pigmentosa progressiva bei Kryoglobulinämie Typ III und Tartrazinintoleranz. Ein Verlauf über 20 Jahre.

A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.