SP0183 DIAGNOSIS AND TREATMENT OF HCV RELATED VASCULITIS
Authors: Peter Lamprecht
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Chronic hepatitis C virus (HCV) infection is the most common cause of cryoglobulinemic vasculitis. In contrast, non-cryoglobulinemic vasculitis is rare in chronic HCV infection. Cryoglobulinemic vasculitis is a systemic immune complex-mediated vasculitis predominantly affecting small vessels and associated with the presence of serum cryoglobulins, i.e. cold-precipitable immunoglobulins. HCV is a hepato- and lymphotropic virus. Notably, secondary transition from benign lymphoproliferative disease to malignant non-Hodgkin lymphoma (NHL) as well as primary co-manifestation of cryoglobulinemic vasculitis and NHL has been reported in chronic hepatitis C. While cryoglobulinemia is detected in 50% or more of the patients with chronic hepatitis C, less than 5% develop related vasculitis. In this disorder, HCV induces clonal proliferation of memory phenotype marginal zone-like B-lymphocytes with restricted Ig heavy chain variable (V<sub>H</sub>) 1-69 gene expression encoding for the IgM rheumatoid factor (RF) WA idiotype. Monoclonal IgM RF binding to the Fc region of polyclonal IgG with anti-HCV reactivity facilitate the formation of cryoprecipitable multi-molecular immune-complexes. Cryoglobulins are preferentially deposited in tissues with high blood flow per unit mass of tissues, <i>e.g.</i> skin, synovium, choroid plexus and glomerulus, where they bind to endothelial cells via the C1q receptor. Endothelial cryoglobulin deposition induces the activation and recruitment of circulating neutrophil granulocytes and other immune cells to the endothelial lesion eventually resulting in complement-consuming vasculitis. The histopathologic changes in HCV-related vasculitis range from cutaneous leukocytoclastic vasculitis to severe necrotizing arteritis. Type I membranoproliferative glomerulonephritis is frequently found in patients with renal involvement. Clinical features of HCV-associated vasculitis comprise purpura, Meltzer`s triad (purpura, arthralgia, asthenia), polyneuropathy, renal involvement and Raynaud`s phenomenon. Hemorrhagic alveolitis, interstitial lung disease, gastrointestinal vasculitis, cardiac involvement, osteosclerosis and hyperviscosity syndrome are less common manifestations. Diagnostic criteria have been developed for HCV-associated cryoglobulinemic vasculitis. International therapeutic guidelines recommend treatment of HCV-related vasculitis to be guided according to the severity of disease. In patients with mild to moderate disease, interferon-free therapy regimens with direct acting antivirals (DAA) are considered as first-line treatment. In patients with severe manifestations, rituximab is given for the control of vasculitic manifestations, followed by HCV eradication using DAA. High rates of clinical responses and sustained virologic responses (SVR) have been reported for DAA treatment in HCV-associated cryoglobulinemic vasculitis. However, relapse of cryoglobulinemic vasculitis may occur in patients despite earlier treatment-induced clinical response and SVR. Persistence of clonal B-lymphocyte proliferation and perseverance of perturbations of the immune homeostasis have been shown in HCV-cured patients with relapse of cryoglobulinemic vasculitis. <h3>Disclosure of Interests:</h3> None declared