Primary cryoglobulinemia is more common in young and middle-aged people, and slightly more common in women than in men. When the patient meets the cold body surface temperature reduction, the precipitation of cryoglobulin in the blood vessels of the extremities or jelly-like, blocking the capillaries, and make the blood vessel wall ischemic necrosis and vasospasm, the skin purpura and cold urticaria is the most common, and some patients can appear Raynaud’s phenomenon. What are the causes of precipitation or jelly-like cold globulin? (I) Pathogenesis Cold globulin is a kind of protein that precipitates in the cold and dissolves when the temperature rises, and it can be divided into 3 types. Type I: is a single-cell line type, i.e. immunoglobulin of monoclonal origin, with four types of IgG, IgM, IgA and cryoglobulin. Type II: is a mixed type, consisting of two or more immunoglobulins, one of which is of monoclonal origin. Type III: is a polyclonal prototype. Type I is not complement-resistant and usually causes large vessel injury by an unknown mechanism. Both types II and III are mixed. (ii) Pathogenesis Anti-complement, through activation of the complement system for immune response and tissue damage, mainly leads to small vessel injury. Abnormally increased cryoglobulins can be categorized into primary and idiopathic according to their sources. The former is asymptomatic and only detected during routine examination, while the latter is often associated with immunoproliferative disorders and infectious diseases.