Renal involvement in essential mixed cryoglobulinemia

Abstract

In the last 20 years, cryoglobulinemia has been found in association with an increasing variety of diseases. Type I cryoglobulins are usually found in myelomas and Waldenstrom's macroglobulinemias. A great percentage of the mixed cryoglobulinemias, which are 60 to 75% of all cryoglobulinemias, are found in connective tissue diseases, in infectious or lymphoproliferative disorders, in hepatobiliary diseases or in immunologically-mediated glomerular diseases, and can therefore be considered 'secondary mixed cryoglobulinemias'. However, for approximately 30% of all mixed cryoglobulinemias the etiology is not clear and the cryoglobulinemia is referred to as 'essential'. The clinical syndrome of essential mixed cryoglobulinemia (EMC) was first described by Meltzer et al in 1966. It was characterized by purpura, weakness, and in some of the patients by glomerular lesions. Many subsequent reports have further defined this syndrome. They also indicate that the incidence of EMC varies in different geographical areas, the majority of cases having been reported in the Mediterranean countries, namely Italy, France, Spain and Israel. They have confirmed that the syndrome can be associated with either type II or type III cryoglobulins. In the rheumatological surveys, patients with type III outnumbered those with type II EMC. On the contrary, surveys based on renal involvement indicated a large prevalence of type II EMC, the monoclonal IgM component being nearly always an IgMk. While the glomerular lesions were variable and non-specific in the few cases of type III EMC with renal involvement, in type II EMC, in which IgMk was the monoclonal component, a particularly well characterized pattern of glomerular disease has been described. We will consider to this special subgroup of patients with type II-EMC in this review, since we think that the description of their renal disease may shed light on the more general problems of the pathogenesis and mechanisms of glomerular and vascular damage in immunologically-mediated renal disease.