Cryoglobulinemia is defined by the presence of circulating immunoglobulins that precipitate at cold temperature and dissolve with rewarming. Cryoglobulinemic vasculitis (CryoVas) is a small-vessel vasculitis involving mainly the skin, the joints, the peripheral nerve system, and the kidneys. Type I cryoglobulins are monoclonal immunoglobulins (mainly IgG or IgM). Type II cryoglobulins consist of a monoclonal immunoglobulin with a rheumatoid factor (RF) activity associated with polyclonal IgG, whereas type III cryoglobulins comprised polyclonal IgM and IgM with RF activity. Type I cryoglobulinemia are related to B-cell lymphoproliferative disorder (Waldenström macroglobulinemia, multiple myeloma, or monoclonal gammopathy of unknown significance), whereas hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas (type II/III).
The 10-year survival rates are 63%, 65%, and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas, and type I CryoVas patients, respectively. In HCV-positive patients, severe liver fibrosis and the five-factor score (FFS) of vasculitis activity were significantly associated with a poor prognosis. In HCV-negative patients, pulmonary and gastrointestinal involvements, renal insufficiency, and age >65 years are independently associated with death. Compared to MGUS, type I CryoVas related to hematologic malignancy tend to be associated with a poorer prognosis.
The treatment of CryoVas is that of the underlying disorder. In type I CryoVas, the treatment is based on that of hemopathy and on specific treatments (plasma exchange and Ilomedine). In HCV-CryoVas with mild to moderate disease, an optimal antiviral interferon-free treatment should be given. For HCV-CryoVas with severe vasculitis (i.e., worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia, cardiac involvement, etc.), the control of disease with rituximab and/or plasmapheresis is often required in addition to the initiation of interferon-free antiviral therapy.
KeywordsCryoglobulins Cryoglobulinemic vasculitis HCV Prognosis Treatment
Antineutrophil cytoplasmic antibodies
Central nervous system
Hepatitis B virus
Hepatitis C virus
Pr Patrice Cacoub has received consultancies, honoraria, advisory board, and speakers’ fees from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Janssen Pharmaceutica, Merck Sharp & Dohme, Pfizer, Roche, Servier, and Vifor Pharma.
Pr Patrice Cacoub is an inventor of a patent application owned by his academic institution and licensed to ILTOO pharma, a biotechnology company developing low-dose IL-2 in autoimmune diseases, in which it holds shares.
Dr Anne Claire has received speakers’ fees from Gilead.
Dr Chloe Comarmond has no conflict of interest.
Dr David Saadoun has received consultancies, honoraria, advisory board, and speakers’ fees from AbbVie, Roche, Bristol-Myers Squibb, and Gilead.
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