Table 1.

Comparison of clinical and laboratory findings between type I and mixed cryoglobulinemia (type II/III)

Type IMixed cryoglobulinemia (type II/III)
Main clinical findings   
 Purpura ∼70% ∼90% 
 Skin ulcers ∼30% ∼15% 
 Glomerulonephritis ∼30% ∼30% 
 Peripheral neuropathy ∼30% ∼30% 
 Arthralgia ∼30% 25%-40% 
 Involvement of lungs, heart, GI tract, and central nervous system Almost never Rare (∼5%) 
 Hyperviscosity syndrome Occasionally; usually in IgM isotype and when M-protein is >4 g/dL Rarely; never in type III 
Laboratory findings   
 Cryoglobulin composition Monoclonal Ig’s (usually IgG or IgM) Type II: monoclonal IgM with RF activity plus polyclonal IgG;Type III: polyclonal IgM with RF activity plus polyclonal IgG 
 Cryocrit Above 5%; can reach more than 50% Less than 5% 
 Complement assays May be decreased Decreased (mainly C4) 
 RF activity Occasionally increased Increased 
Underlying disease   
 Monoclonal gammopathies: MGUS, MM, WM, CLL, non-Hodgkin lymphoma (rarely) HCV, other infections (eg, HBV, HIV, bacterial endocarditis), connective tissue diseases (mainly systemic lupus erythematosis, rheumatoid arthritis, Sjögren's syndrome), hematologic malignancies (WM, other B-cell non-Hodgkin lymphomas, CLL; type II only), unknown (essential mixed cryoglobulinemia) 
Type IMixed cryoglobulinemia (type II/III)
Main clinical findings   
 Purpura ∼70% ∼90% 
 Skin ulcers ∼30% ∼15% 
 Glomerulonephritis ∼30% ∼30% 
 Peripheral neuropathy ∼30% ∼30% 
 Arthralgia ∼30% 25%-40% 
 Involvement of lungs, heart, GI tract, and central nervous system Almost never Rare (∼5%) 
 Hyperviscosity syndrome Occasionally; usually in IgM isotype and when M-protein is >4 g/dL Rarely; never in type III 
Laboratory findings   
 Cryoglobulin composition Monoclonal Ig’s (usually IgG or IgM) Type II: monoclonal IgM with RF activity plus polyclonal IgG;Type III: polyclonal IgM with RF activity plus polyclonal IgG 
 Cryocrit Above 5%; can reach more than 50% Less than 5% 
 Complement assays May be decreased Decreased (mainly C4) 
 RF activity Occasionally increased Increased 
Underlying disease   
 Monoclonal gammopathies: MGUS, MM, WM, CLL, non-Hodgkin lymphoma (rarely) HCV, other infections (eg, HBV, HIV, bacterial endocarditis), connective tissue diseases (mainly systemic lupus erythematosis, rheumatoid arthritis, Sjögren's syndrome), hematologic malignancies (WM, other B-cell non-Hodgkin lymphomas, CLL; type II only), unknown (essential mixed cryoglobulinemia) 

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