Clinical and Experimental Medicine

, Volume 16, Issue 3, pp 233–242 | Cite as

The expanding spectrum of HCV-related cryoglobulinemic vasculitis: a narrative review

  • Franco Dammacco
  • Vito Racanelli
  • Sabino Russi
  • Domenico Sansonno
Review Article

Abstract

Cryoglobulinemic vasculitis (CV) is a small-to-medium-vessel vasculitis that appears in 10–15 % of patients chronically infected with hepatitis C virus (HCV). The classic symptom triad of CV, purpura/asthenia/arthralgia, is accompanied by clinical features that include glomerulonephritis, neuropathy, interstitial pneumonitis, and cardiomyopathy, ranging in their severity from mild to life threatening. The risk of developing non-Hodgkin lymphoma is also higher. The cumulative 10-year survival rate of CV patients is significantly lower than in the age- and sex-matched general population, with death typically caused by nephropathy, malignancies, liver involvement, and severe infections. Unfailing serological stigmata include both a cryoglobulin IgM fraction with rheumatoid factor activity and decreased complement C4 levels. On peripheral B cells, the expression of the CD81 B cell receptor is reduced while that of the CD19 receptor is increased. A monoclonal B cell lymphocytosis develops in almost one-third of patients. HCV-related proteins (but not HCV-RNA genomic sequences) can be detected on biopsy samples by immunofluorescence and immunohistochemistry and involve the vessel lumen, vessel walls, and the perivascular spaces of the skin, kidney, and peripheral nerves, supporting the pathogenetic role of HCV in the onset of a widespread microvasculitis. Based on the demonstration of HCV infection in the large majority of CV patients, a therapeutic regimen consisting of once-weekly pegylated interferon-α and the daily administration of ribavirin results in a sustained virologic response in ~50 % of patients. In those with refractory and relapsing disease, addition of the anti-CD20 monoclonal antibody rituximab has significantly increased the overall response rates. The extension to CV of latest-generation direct-acting antivirals, strikingly successful in non-CV HCV-positive patients, has yielded high complete response rates according to the few studies published thus far.

Keywords

Cryoglobulinemic vasculitis Direct-acting antiviral agents Hepatitis C virus Interferon alpha Mixed cryoglobulinemia Non-Hodgkin lymphoma Rheumatoid factor Rituximab 

Abbreviations

BAFF

B cell activating factor

B-NHL

B cell non-Hodgkin lymphoma

CCR

Complete clinical response

CLL

Chronic lymphocytic leukemia

CS

Corticosteroids

CV

Cryoglobulinemic vasculitis

DAAs

Direct-acting antiviral agents

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

ICs

Immune complexes

LPD

Lymphoproliferative disorder

MC

Mixed cryoglobulinemia

pIFN-α

Pegylated interferon-α

RBV

Ribavirin

RF

Rheumatoid factor

RTX

Rituximab

SVR

Sustained virologic response

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Franco Dammacco
    • 1
  • Vito Racanelli
    • 1
  • Sabino Russi
    • 1
  • Domenico Sansonno
    • 1
  1. 1.Internal Medicine Unit, Department of Biomedical Sciences and Human OncologyUniversity of Bari Medical SchoolBariItaly

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