Mixed cryoglobulinemia syndrome: where are we going to?

Background: Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis of small and medium-sized vessels. Its prevalence presents a large geographic heterogeneity; in particular, MC is more frequent in Southern Europe than in Northern Europe or in Northern America. Because of the striking association between hepatitis C virus (HCV) infection and MCs (up to 95-98% of cases in Italian series), the term 'essential' should be reserved only to the small number of patients without overt infectious, immuno-rheumatological or neoplastic disorders.Several strategies have been adopted to contrast HCV infection, such as the screening of hemoderivatives and the development of antiviral therapies.Objectives: we investigated the possible variations during the last years of the prevalence of HCV infection in Italian patients with overt MCs.Methods: From 2000 to 2008, MCs was diagnosed for the first time in 75 consecutive patients referred to our Rheumatology Unit (55F and 20M; mean age 65.7\ub111.3 SD years). At the beginning of the follow-up, all patients showed clinico-serological and pathological features sufficient for the a definite diagnosis of MCs according to the preliminary classification criteria.They were characterized by the typical clinical triad -purpura, weakness, arthralgias- in 80% of patients, mild-moderate chronic hepatitis in 52%, peripheral neuropathy in 65%, nephropathy in 9%, and severe cutaneous vasculitis in 21%.Results: in the present series of recently diagnosed patients, the percentage of HCV-positive individuals (81.3%; genotype 1b 55%, 2a/2c 38%; other 7%) was lower compared to previously observed prevalence of HCV-positives (92%) in our 168 patients screened for HCV infection. We can speculate that this reduction could be the result of several actions adopted in order to reduce the incidence of HCV infection in the general population. Furthermore, the use of combined antiviral treatment, particularly if introduced in the early stages of infection, increases the percentage of HCV eradication and, consequently, it reduces the risk of developing MCs. On the other hand, the populations with a higher prevalence of HCV infection (i.e. Africans or Asians) more often are infected with viral genotypes that seem to be scarcely involved in the pathogenesis of MCs.Another important finding of the present series is the patients' age at the diagnosis compared to that observed in our previous study (65.7\ub111.3 vs 56\ub111 SD years; p