title: Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients.
abstract: OBJECTIVE
  The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion.
  
  
  METHODS
  Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements.
  
  
  RESULTS
  An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides.
  
  
  CONCLUSIONS
  Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.
authors.affiliation: Medicina Interna, Department of Medicine, Surgery and Dentistry, Policlinico San Marco of Zingonia, University of Milan, Italy.
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authors.lastname: Pietrogrande
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authors.forename: Piero
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authors.lastname: Montecucco
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authors.forename: Felice
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authors.forename: Massimo
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authors.forename: Piersandro
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authors.lastname: Riboldi
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authors.forename: Dario
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authors.lastname: Scarpato
authors.forename: Renato
authors.initials: R
authors.lastname: Sinico
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.forename: Antonio
authors.initials: A
authors.lastname: Tavoni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bonacci
authors.forename: Piero
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authors.lastname: Renoldi
authors.forename: Davide
authors.initials: D
authors.lastname: Filippini
authors.forename: Piercarlo
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authors.lastname: Sarzi-Puttini
authors.forename: Clodoveo
authors.initials: C
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mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001781:Blood Component Removal; D003449:Cryoglobulinemia / Q000209:etiology / Q000628:therapy*; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005938:Glucocorticoids / Q000627:therapeutic use; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D000069283:Rituximab; D014779:Virus Replication / Q000187:drug effects
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069283:Rituximab; C100416:peginterferon alfa-2a