The diagnosis and classification of the cryoglobulinemic syndrome

Cryoglobulinemia refers to the presence of reversible precipitation of immunoglobulins in the blood upon exposure to reduced (body) temperature. In clinical practice, the detection and typing of cryoglobulins appear to be poorly standardized. A consensus protocol for detection and typing of cryoglobulins, as extracted from the literature, is presented. Items that require further standardization are discussed. Cryoglobulins may cause clinical symptoms due to either obstruction of the small blood vessels, in particular in the extremities that are more exposed to the cold, or vascular inflammation due to the deposition of immune complexes. Only for the latter situation, i.e. cryoglobulinemic vasculitis in the presence of mixed-type cryoglobulinemia, preliminary classification criteria have been defined. Besides the presence of cryoglobulins, at least two of three items have to be present. These items include a restricted number of self-reported clinical history, typical clinical manifestations, and specified laboratory findings. These classification criteria await further validation in an independent patient cohort.