Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients

Maurizio Pietrogrande, Salvatore De Vita, Anna Linda Zignego, Pietro Pioltelli, Domenico Sansonno, Salvatore Sollima, Fabiola Atzeni, Francesco Saccardo, Luca Quartuccio, Savino Bruno, Raffaele Bruno, Mauro Campanini, Marco Candela, Laura Castelnovo, Armando Gabrielli, Giovan Battista Gaeta, Piero Marson, Maria Teresa Mascia, Cesare Mazzaro, Francesco MazzottaPierluigi Meroni, Carlomaurizio Montecucco, Elena Ossi, Felice Piccinino, Daniele Prati, Massimo Puoti, Piersandro Riboldi, Agostino Riva, Dario Roccatello, Evangelista Sagnelli, Patrizia Scaini, Salvatore Scarpato, Renato Sinico, Gloria Taliani, Antonio Tavoni, Eleonora Bonacci, Piero Renoldi, Davide Filippini, Piercarlo Sarzi-Puttini, Clodoveo Ferri, Giuseppe Monti, Massimo Galli

Research output: Contribution to journalArticlepeer-review


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. Conclusion: 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.

Original languageEnglish
Pages (from-to)444-454
Number of pages11
JournalAutoimmunity Reviews
Issue number8
Publication statusPublished - Jun 2011


  • Apheresis
  • Cryoglobulinemia
  • Cyclophosphamide
  • Glucocorticoids
  • HCV
  • Mixed cryoglobulinemia syndrome
  • Pegylated interferon
  • Ribavirin
  • Rituximab

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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