cryoglobulin

Cryoglobulin refers to immunoglobulins that precipitate at temperatures below normal body temperature and dissolve upon warming. The presence of cryoglobulins in serum can lead to cryoglobulinemia, a small-vessel vasculitis caused by immune complex deposition in capillaries and venules. Cryoglobulins are classified into three main types based on immunoglobulin composition: type I involves a single monoclonal immunoglobulin (usually IgM or IgG) and is often associated with hematologic malignancies such as multiple myeloma or Waldenström macroglobulinemia; type II is a mixed cryoglobulinemia with a monoclonal IgM with rheumatoid factor activity and polyclonal IgG; type III is a mixed cryoglobulinemia with polyclonal IgM and IgG. Type II and III are commonly linked to chronic infections or autoimmune diseases, most notably hepatitis C virus infection for type II and various autoimmune conditions for type III.

Clinical features commonly include a triad of palpable purpura, arthralgia or arthritis, and fatigue or weakness. Other manifestations may involve neuropathy, renal disease (often membranoproliferative glomerulonephritis with proteinuria and hematuria), and less frequently liver involvement or central nervous system symptoms. Laboratory findings typically show detectable cryoglobulins, hypocomplementemia with low C4, positive rheumatoid factor, and a positive test for underlying infections or autoimmune diseases. Hepatitis C infection is especially associated with mixed cryoglobulinemia.

Diagnosis relies on detecting cryoglobulins in serum, a process requiring careful sample handling (blood kept at body temperature during collection and serum refrigeration to allow cryoprecipitation). Additional testing includes immunofixation to type the cryoglobulins, quantification of immunoglobulins, complement levels, and screening for infections such as hepatitis C.

Treatment targets the underlying cause and the vaso-occlusive manifestations. Antiviral therapy for hepatitis C improves outcomes in many cases of mixed cryoglobulinemia; immunosuppressive therapy or rituximab may be used for vasculitic symptoms, and plasmapheresis can be considered for severe, life-threatening disease. Patients are advised to avoid cold exposure to prevent cryoprecipitation.