Introduction: The clinical and therapeutic management of mixed cryoglobulinemia (MC)
remains a subject of controversy. In addition, most studies have not recorded the long-term follow-up
and the outcome of these cases. Material and Methods: We enrolled 246 patients affected by MC who
were consecutively admitted to our Department from January 1993 to February 2013. Clinical and
biological data had been recorded until June 2014. Results: The median age (at diagnosis) was
60 years (range 26–83). The aetiology was HCV in 95% of patients, HBV in 3% and “essential” in
2%. HCV genotype was 1b in 57%, genotypes 2–3 in 43%. MC was Type II in 203 of the cases
(87%) and Type III in 52 (13%). The most frequent clinical manifestations were purpura (72%),
chronic liver disease (70%), glomerulonephritis (35%), arthralgias (58%), peripheral neuropathy
(21%), non-Hodgkin lymphoma (15%) and cutaneous ulcers (3%). Purpura, arthralgias, peripheral
neuropathy, glomerulonephritis and non-Hodgkin lymphoma were more frequently observed in Type
II than in Type III MC (p < 0.05). Treatments were interferon (IFN) or Pegilated-IFN (PEG-IFN) alone
or plus Ribavirin (RIBA) in 101 cases, steroids with or without alkylating agents in 33 cases, Rituximab
in 8 patients. The complete clinical, virological and immunological responses were associated with
PEG-IFN plus RIBA. Severe infections were associated with renal failure. At 10 years, the overall
survival rate was 71% in Type II MC and 84% in Type III (p < 0.053). Conclusions: From our data,
antiviral therapy is the first-line therapy in HCV-related MC, whereas steroids, alkylating agents and
Rituximab should be considered as a second-line therapy. Given the heterogeneity of the disease,
the role of these different therapeutic strategies should be checked in randomized controlled trials.
