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Cryoglobulinemic Vasculitis

  • Anne Claire Desbois
  • Cloe Comarmond
  • David Saadoun
  • Patrice Cacoub
Chapter

Abstract

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.

Keywords

Cryoglobulins Cryoglobulinemic vasculitis HCV Prognosis Treatment 

Abbreviations

ANCA

Antineutrophil cytoplasmic antibodies

CMV

Cytomegalovirus

CNS

Central nervous system

CryoVas

Cryoglobulinemic vasculitis

FFS

Five-factor score

HBV

Hepatitis B virus

HCV

Hepatitis C virus

PEG-IFN

Pegylated interferon

RBV

Ribavirin

RF

Rheumatoid factor

Notes

Funding Sources

None.

Disclosure

  • 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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anne Claire Desbois
    • 1
    • 2
    • 3
    • 4
  • Cloe Comarmond
    • 1
    • 2
    • 3
    • 4
  • David Saadoun
    • 1
    • 2
    • 3
    • 4
  • Patrice Cacoub
    • 1
    • 2
    • 3
    • 4
  1. 1.Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B)ParisFrance
  2. 2.INSERM, UMR_S 959ParisFrance
  3. 3.CNRS, FRE3632ParisFrance
  4. 4.AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Referral Center for Rare Autoimmune Systemic DisordersParisFrance

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