Table 1

Classification and clinico-pathological characteristics of different cryoglobulinemias.


Composition
Pathological findings
Clinical associations

Type I cryoglobulinemia
monoclonal Ig, mainly IgG, or IgM, or IgA
self-aggregation through Fc fragment of Ig
tissue histological alterations of underlying disorder
-lymphoproliferative disorders: MM, WM, CLL, B-cell NHL
Type II
mixed cryoglobulinemia
monoclonal IgM (or IgG, or IgA) with RF activity (often cross-idiotype WA-mRF) and polyclonal Ig (mainly IgG)
-leukocytoclastic vasculitis
-B-lymphocyte expansion with tissue infiltrates
-infections (mainly HCV)
-autoimmune/lymphoproliferative disorders
-rarely 'essential'
Type II–III
mixed cryoglobulinemia
oligoclonal IgM RF or mixture of poly/monoclonal IgM
(often cross-idiotype WA-mRF)
-leukocytoclastic vasculitis
-B-lymphocyte expansion with tissue infiltrates
-infections (mainly HCV)
-autoimmune/lymphoproliferative disorders
-rarely 'essential'
Type III
mixed cryoglobulinemia
polyclonal mixed Ig (all isotypes) with RF activity of one polyclonal component (usually IgM)
-leukocytoclastic vasculitis
-B-lymphocyte expansion with tissue infiltrates
-infections (mainly HCV)
-more often autoimmune disorders
-rarely 'essential'

lymphoproliferative disorders: MM (multiple myeloma), WM (Waldenstrom's macroglobulinemia), chronic lymphocytic leukemia), B-cell non-Hodgkin's lymphoma;

Ig: immunoglobulin; RF: rheumatoid factor; HCV: hepatitis C virus

Ferri Orphanet Journal of Rare Diseases 2008 3:25   doi:10.1186/1750-1172-3-25