Patient characteristics of HCV-negative mixed cryoglobulinemia (MC) in Italy and Holland

A striking association between Mixed Cryoglobulinemia (MC) and Hepatitis C Virus (HCV) infection has already been established by means of clinico-epidemiological and laboratory studies. The HCV-associated MC is more common in Southern Europe than in Northern Europe or Northern America; it is probably due to the endemic presence of HCV infection, as well as to unknown environmental and/or predisposing genetic co-factors. The etiopathogenesis and epidemiology of HCV-negative MC, an heterogeneous group of diseases consisting of a small number of 'essential' MC, various autoimmune-lymphoproliferative disorders and MC associated with infectious agents of scarce clinical relevance, remain still widely unknown. While HCV represents the major etiological agent of MC in the Mediterranean area, particularly in Italy, patients with HCV-negative MC are more frequent in areas where the overall prevalence of the disease is significantly low and less frequent its association with HCV.The purpose of this study is to compare patients with HCV-negative MC type II followed in Italy with Dutch patient's series with regard to their clinical characteristics and associated disorders.Overall clinical characteristics of HCV-negative MC are similar to that recorded in different patient's series of the HCV-positive MC except a lower percentage of purpura (52% vs 81%). No differences between Italian and Dutch patients were uncovered in this study except that nephropathy is significantly more frequent in Holland. The diagnosis of essential HCV-negative MC is more frequent in Holland than in Italy (42% versus 18%). These data suggest that one or more unknown infectious agent might be implicated in the etiopathogenesis of Dutch EMC patients. Finally, ‘essential’ MC represent a charming challenge for future etiopathogenetic studies.