Diagnostics and Treatment of Cryoglobulinaemia: It Takes Two to Tango

Jan Damoiseaux*, Jan Willem Cohen Tervaert

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Cryoglobulins are immunoglobulins that reversibly precipitate in the cold. They come in different flavours and, as such, are differentially associated with lymphoproliferative diseases (type I), or systemic autoimmune diseases, and/or infectious diseases (type II/III). The clinical manifestations of cryoglobulinaemia result from either hyper-viscosity or small vessel vasculitis. Hepatitis C virus (HCV) is a well-known factor in the aetiology of cryoglobulinaemia, but substantial geographical differences exist in the association between cryoglobulins and HCV. In the absence of any underlying disease, cryoglobulinaemia is referred to as 'idiopathic' or 'essential'. Detection of cryoglobulins in the laboratory is hampered by several pitfalls, in particular in the pre-analytical stage as well as in the quantification. In addition, our personal experience reveals that the detection of rheumatoid factor, most often present in high concentrations in patients with mixed cryoglobulinaemia, relies on the choice of the test system. Hence, interpretation of the laboratory results in relation to the clinical manifestations requires a partnership between the clinician and the laboratory specialist in order to make a correct diagnosis. Treatment options are primarily directed by identification of underlying diseases, i.e. infections or systemic autoimmune diseases. Idiopathic cryoglobulinaemia is treated with corticosteroids and immunosuppression, or B cell depleting anti-CD20 biologicals. In this overview, the recent literature on current laboratory and clinical practice of cryoglobulinaemia is discussed from a personal perspective.
Original languageEnglish
Pages (from-to)299-310
JournalClinical Reviews in Allergy & Immunology
Issue number3
Publication statusPublished - Dec 2014


  • Cryoglobulin
  • Vasculitis
  • Rheumatoid factor
  • Hepatitis C virus

Cite this