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Cryoglobulinemia: an update in 2019

Joint, bone, spine : revue du rhumatisme | 8 Feb 2019

AC Desbois, P Cacoub and D Saadoun
Abstract
Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II cryoglobulinemia), or only of polyclonal Igs (mixed type III cryoglobulinemia). The manifestations of type I cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin’s lymphoma. The treatment depends mainly on the cause of the cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I cryoglobulinemia.
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