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Cryoglobulinaemia

Nature Reviews Disease Primers volume 4, Article number: 11 (2018) Cite this article

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Abstract

Cryoglobulinaemia refers to the serum presence of cryoglobulins, which are defined as immunoglobulins that precipitate at temperatures <37 °C. Type I cryoglobulinaemia consists of only one isotype or subclass of monoclonal immunoglobulin, whereas type II and type III are classified as mixed cryoglobulinaemia because they include immunoglobulin G (IgG) and IgM. Many lymphoproliferative, infectious and autoimmune disorders have been associated with mixed cryoglobulinaemia; however, hepatitis C virus (HCV) is the aetiologic agent in most patients. The underlying mechanism of the disorder is B cell lymphoproliferation and autoantibody production. Mixed cryoglobulinaemia can cause systemic vasculitis, with manifestations ranging from purpura, arthralgia and weakness to more serious lesions with skin ulcers, neurological and renal involvement. This Primer focuses on mixed cryoglobulinaemia, which has a variable course and a prognosis that is primarily influenced by vasculitis-associated multiorgan damage. In addition, the underlying associated disease in itself may cause considerable mortality and morbidity. Treatment of cryoglobulinaemic vasculitis should be modulated according to the underlying associated disease and the severity of organ involvement and relies on antiviral treatment (for HCV infection), immunosuppression and immunotherapy, particularly anti-CD20 B cell depletion therapies.

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Fig. 1: Classification of cryoglobulinaemia based on immune typing.
Fig. 2: Mechanisms of HCV-related cryoglobulinaemia vasculitis.
Fig. 3: The clinical, serological and pathological hallmarks of cryoglobulinaemic vasculitis.
Fig. 4: Renal pathology in cryoglobulinaemic vasculitis.
Fig. 5: Clinical overlap between HCV-related conditions and autoimmune diseases.
Fig. 6: Skin ulcers in severe cryoglobulinaemic vasculitis.

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Reviewer information

Nature Reviews Disease Primers thanks F. Dammacco, Y. Shoenfeld, L. Quartuccio and the other anonymous referee(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Center of Research of Immunopathology and Rare Diseases—CMID, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, and Nephrology and Dialysis Division (ERKnet member), Department of Clinical and Biological Sciences of the University of Turin, and San Giovanni Bosco Hospital, Turin, Italy

    Dario Roccatello

  2. Sorbonne Universités, UPMC Université Paris, Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), Paris, France

    David Saadoun

  3. AP HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, National Center for Autoimmune and Systemic Diseases and for Autoinflammatory Diseases, Paris, France

    David Saadoun

  4. Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain

    Manuel Ramos-Casals

  5. Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain

    Manuel Ramos-Casals

  6. Department of Medicine, University of Barcelona, Barcelona, Spain

    Manuel Ramos-Casals

  7. Department of Pathophysiology and Joint Academic Rheumatology Program, Medical School of the National and Kapodistrian University of Athens, Athens, Greece

    Athanasios G. Tzioufas

  8. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    Fernando C. Fervenza

  9. Hôpital La Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France

    Patrice Cacoub

  10. Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Anna Linda Zignego

  11. Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Modena, Italy

    Clodoveo Ferri

Authors
  1. Dario Roccatello
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  2. David Saadoun
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  3. Manuel Ramos-Casals
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  4. Athanasios G. Tzioufas
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  5. Fernando C. Fervenza
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  6. Patrice Cacoub
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  7. Anna Linda Zignego
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  8. Clodoveo Ferri
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Contributions

Introduction (D.R.); Epidemiology (A.G.T.); Mechanisms/pathophysiology (D.R. and P.C.); Diagnosis, screening and prevention (C.F. and D.S.); Management (F.C.F., M.R.-C. and A.L.Z.); Quality of life (M.R.-C.); Outlook (D.R.); Overview of Primer (D.R.).

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Correspondence to Dario Roccatello.

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Roccatello, D., Saadoun, D., Ramos-Casals, M. et al. Cryoglobulinaemia. Nat Rev Dis Primers 4, 11 (2018). https://doi.org/10.1038/s41572-018-0009-4

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