Cold globulinemia, first of all, we need to understand what is cold globulin, cold globulin is a substance that naturally precipitates from serum or plasma at a low temperature of 4°C and then dissolves when heated to 37°C. It is mainly composed of immunoglobulin and complement. When cold globulin is present in the blood, it is called cold globulinemia. Broadly speaking it is also a systemic vasculitis caused by immune complexes containing cryoglobulins, it is divided into three types, type I monoclonal cryoglobulins, type II mixed monoclonal and polyclonal cryoglobulins. Type III mixed polyclonal cold globulin. Not all cryoglobulinemia has clinical symptoms, and about more than 50% of type I and 15% of type II have no clinical symptoms. First, the main clinical manifestations include red rash of palpable purpura on the lower extremities; second, there can be joint and muscle symptoms, such as arthralgia and muscle weakness; third, there can be neurological damage, mainly manifested as sensory and motor impairment caused by peripheral nerve damage; fourth, there can also be renal damage, and its treatment mainly includes, in mild cases, no special treatment is needed, that is, symptomatic treatment. For severe cases, plasma exchange can be considered or other immunosuppressive treatments can be actively taken.