What are cryoglobulins anyway?

Cryoglobulinemia….we love to have it on our differential, but what are cryoglobulins? Per Dr. Vadia, if you understand cryoglobulins, you understand medicine….so here you go!

  • Cryoglobulins are proteins, either immunoglobulins or a mixture of immunoglobulins and complement components
  • Cryoglobulinemia refers to the presence of CG in a patient’s serum, although it is usually used to imply the systemic inflammatory syndrome that generally involves small-to-medium vessel vasculitis due to CG-containing immune complexes
  • Clinically-significant cryoglobulinemia may be present in about 1 in 100,000, however, chronic infections and inflammatory states may have detectable levels of CGs without clinical pathology: 15-20 % in HIV infection, 15-20 % in CTD, 40-65 %in hepatitis C. This means that pathogenic elevations in CG may be due to over-proliferation (inflammation, hyper-proliferative states, increase complex formation or decreased clearance).
  • Most commonly, CGs consist of autoantibodies with rheumatoid factor activity, suggesting an antigen-independent, hyperproliferative etiology (CLINICAL PEARL, consider screening for cryoglobulins with RF and Complements – although RF may be negative in the less common type I cryoglobulins associated with lymphoproliferative disorders)
  • Clinical symptoms are variable but may include:
    • Skin – often palpable purpura but may also present as ulcers, livideo reticularis, raynaud’s and acrocyanosis
    • Musculoskeletal – typically arthralgias and myalgias but frank arthritis or myositis is rare to uncommon
    • Neuropathy – peripheral neuropathy by EMG due to vascultitis is common, however clinically significant neuropathy is uncommon
    • Pulmonary – pulmonary symptoms such as dyspnea, cough and pleurisy may be common, but BOOP, pulmonary hemnorrhage and pulmonary vasculitis are rare
    • Renal – often due to immune complex formation leading to glomerulonephritis but may range from isolated proteinuria and hematuria to nephrotic or nephritic syndromes
  • Diagnosis – serum must be collected at 37 degrees C. The sample must then be transferred at that temp, allowed to clot for 30 mins at that temp and centrifuged at that temp. Later, the sample will be cooled to allow for cryo precipitation and then measured (not easy, see clinical pearl above)