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Mixed cryoglobulinaemia after hepatitis C virus: more and less ambiguity
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Since the discovery of the association of hepatitis C virus (HCV) with mixed cryoglobulinaemia, the use of this term is more ambiguous than ever on the one hand; on the other hand, there is less ambiguity as 80% of what previously was classified as essential mixed cryoglobulinaemia (EMC) is now known as secondary to HCV infection. The ambiguity is generated mainly by the heterogeneity of mixed cryoglobulins that were originally defined as containing IgG- anti-IgG (rheumatoid factor (RF)) immune complexes. Early studies focused on these RF containing mixed cryoglobulins; most of the recent studies, which are predominantly studies on patients with HCV infection, include cryoglobulins characterised for mixed isotypes of immunoglobulins but not for RF activity.
Meltzer, Franklin and colleagues1 first coined the term
"mixed cryoglobulins" for the cryoglobulinaemia composed of IgG and
IgM RF that accompanied the syndrome of palpable purpura, arthralgias,
and weakness. Studies performed by Franklin's group
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