Three subtypes of cryoglobulins are characterized, according to immunoglobulin type:
- Type I cryoglobulins (10%-15% of cases) are monoclonal cryoglobulins typically made of IgM and sometimes IgA or IgG. Type I cryoglobulinemia is associated with lymphoproliferative disorders (most commonly multiple myeloma and Waldenström macroglobulinemia). The monoclonal cryoglobulins precipitate at lower temperatures, leading to vascular occlusion and ischemic damage of tissues. Typically, acral areas are affected.
- Type II (50%-60% of cases) and Type III (30%-40% of cases) cryoglobulins are mixed cryoglobulins that consist of a rheumatoid factor (IgM) complexed with either a monoclonal IgG (Type II) or a polyclonal IgG or non-immunoglobulin serum component (Type III). While mixed cryoglobulins are most commonly associated with infections (hepatitis B and C, Epstein-Barr virus, cytomegalovirus, leprosy, endocarditis, and more rarely parasitic infections) and rheumatological conditions (systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome), lymphoproliferative diseases (such as chronic lymphocytic leukemia) have also been associated. These complexes cause a small and medium vessel vasculitis due to deposition of IgG/IgM and complement activation.
D89.1 – Cryoglobulinemia
30911005 – Cryoglobulinemia
- Cryofibrinogenemia – Cold precipitable proteins are found in plasma but not in serum.
- Cholesterol emboli
- Bacterial sepsis
- Coumadin necrosis
- Purpura fulminans
- Cocaine levamisole toxicity
- Raynaud disease
- Waldenström macroglobulinemia
- Livedoid vasculopathy
- Chilblains (perniosis)
- Heparin-induced thrombocytopenia
- Thrombotic thrombocytopenic purpura / hemolytic uremic syndrome
- Protein C and protein S deficiencies
- Antithrombin III deficiency
- Prothrombin G202120A mutation
- Factor V Leiden deficiency
- Sickle cell disease