Wintrobe and Buell<sup>228Wintrobe M.M., Buell M.V. Hyperproteinemia associated with multiple myeloma Bulletin of the Johns Hopkins Hospital 1933 ;  52 : 156

Cliquez ici pour aller à la section Références</sup> first described reversible cryoprecipitability of serum in a patient with multiple myeloma in 1933. Lerner systematically studied cold-induced precipitation of these immunoglobulins, and in 1947 Lerner and Watson<sup>128Lerner A.B., Watson C.J. Studies of cryoglobulins. Unusual purpura associated with the presence of a high concentration of cryoglobulin (cold precipitable serum globulin) Am J Med Sci 1947 ;  2 : 410 [cross-ref]

Cliquez ici pour aller à la section Références</sup> first employed the term cryoglobulins. In the 1960s, the clinical studies of Meltzer and others<sup>146Meltzer M., Franklin E.C. Cryoglobulinemia–a study of twenty-nine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability Am J Med 1966 ;  40 : 828 [cross-ref]

Cliquez ici pour aller à la section Références, 147Meltzer M., Franklin E.C., Elias K., et al. Cryoglobulinemia–a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity Am J Med 1966 ;  40 : 837 [cross-ref]

Cliquez ici pour aller à la section Références</sup> delineated a distinct syndrome of purpura, arthralgias, asthenia, and renal disease–often in the context of immune complex deposition or vasculitis. By 1974, Brouet et al<sup>17Brouet J.C., Clauvel J.P., Danon F., et al. Biologic and clinical significance of cryoglobulins. A report of 86 cases Am J Med 1974 ;  57 : 775 [cross-ref]

Cliquez ici pour aller à la section Références</sup> popularized a system which classified cryoglobulinemia by the components of the cryoprecipitate: type I, isolated monoclonal immunoglobulins; type II, a monoclonal component, usually immunoglobulin M (IgM), possessing activity toward polyclonal immunoglobulins, usually immunoglobulin G (IgG); and type III, polyclonal immunoglobulins of more than one isotype. This classification provided a framework for clinical correlations.

Associated conditions, such as lymphoproliferative disorders, connective tissue disorders, infection, liver disease and others listed in the box on the following page, were observed in some<sup>92Gorevic P.D., Kassab H.J., Levo Y., et al. Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients Am J Med 1980 ;  69 : 287 [cross-ref]

Cliquez ici pour aller à la section Références, 105Hurwitz D., Quismorio F.P., Friou G.J. Cryoglobulinaemia in patients with infectious endocarditis Clin Exp Immunol 1975 ;  19 : 131

Cliquez ici pour aller à la section Références, 199Seligmann M., Danon F., Basch A., et al. IgG myeloma cryoglobulin with antistreptolysin activity Nature 1968 ;  220 : 711

Cliquez ici pour aller à la section Références, 218Turkington R.W., Buckley C.E. Macrocryoglobulinemia and sarcoidosis Am J Med 1966 ;  40 : 156

Cliquez ici pour aller à la section Références, 225Weisman M., Zvaifler N. Cryoglobulins in rheumatoid arthritis Rheumatology (Basel) 1975 ;  6 : 60

Cliquez ici pour aller à la section Références</sup> but not all patients.

In several large series, 34% to 71% of cases of cryoglobulinemia were not associated with other disease states; these were termed essential or primary cryoglobulinemia (Table 1).<sup>17Brouet J.C., Clauvel J.P., Danon F., et al. Biologic and clinical significance of cryoglobulins. A report of 86 cases Am J Med 1974 ;  57 : 775 [cross-ref]

Cliquez ici pour aller à la section Références, 92Gorevic P.D., Kassab H.J., Levo Y., et al. Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients Am J Med 1980 ;  69 : 287 [cross-ref]

Cliquez ici pour aller à la section Références, 158Monti G., Galli M., Invernizzi F., et al. Italian Group for the Study of Cryoglobulinemias Cryoglobulinaemias: A multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease Q J Med 1995 ;  88 : 115

Cliquez ici pour aller à la section Références</sup> Following its identification in the late 1980s, the hepatitis C virus (HCV) was recognized to be a potential causative factor for essential mixed cryoglobulinemia (EMC).<sup>66Ferri C., Greco F., Longombardo G., et al. Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia Arthritis Rheum 1991 ;  34 : 1606

Cliquez ici pour aller à la section Références, 174Pascual M., Perrin L., Giostra E., et al. Hepatitis C virus in patients with cryoglobulinemia type II J Infect Dis 1990 ;  162 : 569 [cross-ref]

Cliquez ici pour aller à la section Références</sup> This association has been confirmed by a number of groups since its original description in 1990. The mechanism of HCV involvement in mixed cryoglobulinemia (MC) and its potential role in the development of other autoimmune diseases and non-Hodgkin's