Vasculitic syndromes in hepatitis C virus: A review

Abstract

Vasculitis is a remarkable presentation of the extrahepatic manifestations of HCV. According to the presence or absence of cryoglobulins it is subdivided into two main types: cryoglobulinemic vasculitis and non cryoglobulinemic vasculitis based on the attribution of vasculitis to serum cryoglobulins as a pathogenic factor. The attribution of cryoglobulinemia to HCV represents a success story in the history of immunology, microbiology, and clinical medicine. HCV can bind to and invade lymphocytes, consequently triggering an immune response through different mechanisms. The epidemiology of the disease is well described and the clinical picture describes cutaneous, pulmonary, musculoskeletal, neurological, renal, endocrine, gastrointestinal, hepatic and cardiovascular manifestations. It may also be associated with sicca symptoms, an increased risk of lymphoma and serious catastrophic events. The pathology is well characterized. A classification criteria of the syndrome that was validated in 2014 is discussed. Management of CV is decided according to the presence and severity of its clinical presentation. It is divided into asymptomatic, mild, moderate, severe and life threatening disease. Recently introduced direct antiviral agents are proving safe and effective in the management of cryoglobulinemic vasculitis, and it is advocated that the two types of vasculitis be given prioritization in the Egyptian mass campaign to eradicate HCV.

Keywords: ANCA, antineutrophil cytoplasmic antibody; APS, antiphospholipid syndrome; BAL, bronchoalveolar lavage; CAPS, catastrophic antiphospholipid syndrome; CRP, C reactive protein; CTD, connective tissue disease; Cryoglobulins; DAA, direct acting antiviral drugs; Direct acting anti-HCV drugs; ESR, erythrocyte sedimentation rate; Extrahepatic manifestations vasculitis; GIT, gastrointestinal tract; HSP, Henoch-Schonlein Purpura; HUS, hemolytic uremic syndrome; Hepatitis C virus; IFN α, interferon alpha; IHD, ischemic heart disease; MOH, minister of health; MRI, magnetic resonance imaging; NHL, non Hodgkin lymphoma; PAN, polyarteritis nodosa; PCR, polymerase chain reaction; PFT, pulmonary function test; PN, peripheral neuropathy; RNA, ribonucleic acid; TIAs, transient ischemic attacks; TTP, thrombotic thrombocytopenic purpura.

Graphical abstract

Fig. 1

Three cases with cutaneous manifestations of CV: a) Hyperpigmented skin lesions, b) Finger gangrene, and c) Livedo reticularis.

Fig. 2

Skin biopsy from a purpuric lesion shows (a) Marked extravasation of red blood cells, (b) a dense perivascular infiltrate of neutrophils and lymphocytes, and (c) thickening of blood vessel wall with fibrin deposition, a perivascular infiltrate with neutrophils show leukocytoclasia (Courtesy of Dr Hussein Hassab-ElNaby Professor of Dermatology and Dermatopathology Al-Azhar University).

Fig. 3

Skin biopsy from a vesicular lesion shows (a) A subepidermal cleft, (b) the cleft contains neutrophils, and (c) a perivascular infiltrate of neutrophils with blood vessel wall necrosis (Courtesy of Dr Hussein Hassab-ElNaby Professor of Dermatology and Dermatopathology Al-Azhar University).

Fig. 4

A case of HCV related Glomerulonephritis (Cryoglobulinemic GN). It shows (a) irregular thickening of capillary basement membrane (GBM) with wire loop formation (thick arrows) and segmental proliferation (thin arrow). Hx and E, original magnifications × 400 and (b) wire loop formation, hyaline thrombi and segmental proliferation (arrows). Hx and E × 400. (Courtesy of Dr Sawsan Fadda Professor of Pathology Cairo University).

Fig. 5

(a) Another case shows irregular thickening of GBM with formation of PAS positive hyaline thrombi (arrows). PAS stain × 400 and (b) a third case show wire loop formation (thick arrows) and hyaline thrombi (thin arrows). Masson Trichrome stain × 400 (Courtesy of Dr Sawsan Fadda Professor of Pathology Cairo University).

Fig. 6

Management of CV. Adapted and modified from Cacoub et al. .

Fig. 7

One of our patients with CV and leg ulcer before (a) and after (b) treatment with sofosbuvir, Ribavirin, and IFN combination.

Fig. 8

Vasculitic lesions in one of our patients with HCV related PAN showing: (a) Foot necrotizing ulcers, (b) Acral gangrene, and (c) Healed necrotizing ulcers.