Classification of Cryoglobulinemia

●The Brouet classification criteria is the most commonly used system that classifies cryoglobulinemia into three different subgroups based on their Ig composition. These classification criteria are also useful in that the subgroups partly correlate with pathogenicity and clinical manifestations.

•In type I cryoglobulinemia, the cryoglobulins are monoclonal Ig, typically IgG or IgM, and less commonly IgA or free Ig light chains. Type I cryoglobulinemia develops in the setting of protein-secreting monoclonal gammopathies such as a monoclonal gammopathy of undetermined significance (MGUS) or a B-cell lineage malignancy (eg, multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia).

•In type II cryoglobulinemia, the cryoglobulins are composed of a mixture of a monoclonal IgM (or IgG or IgA) with rheumatoid factor (RF) activity and polyclonal Ig. Type II cryoglobulins are often associated with persistent viral infections, particularly hepatitis C virus (HCV) infection, and are associated with the mixed cryoglobulinemia syndrome. Other clinical associations with type II cryoglobulinemia include other infections such as hepatitis B virus (HBV), HIV, autoimmune diseases (mainly systemic lupus erythematosus [SLE] and Sjögren's syndrome), and lymphoproliferative disorders.

•In type III cryoglobulinemia, the cryoglobulins are composed of a mixture of polyclonal IgG (all isotypes) and polyclonal IgM. These cases are often secondary to autoimmune disorders, but can also be associated with infections (mainly HCV).

Bhopalwala. H