Page 53 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 29

malignancies. The commonest clinical manifestations of HCV- negative MC vasculitis in the
CryoVas survey [107] included purpura (75%), peripheral neuropathy (52%), arthralgia or
arthritis (44%), glomerulonephritis (36%), cutaneous ulcers (16%), and cutaneous necrosis
(14%). A connective tissue disease was diagnosed in 30% of patients, and B-cell non-
Hodgkin lymphoma (B-NHL) was noted in 22% of patients, whereas MCV was considered
essential in 48% of patients. There was a greater frequency of joint involvement (53% versus
40%), peripheral neuropathy (74% versus 52%), CNS involvement (9% versus 2%) in those
with HCV-MC compared to those with HCV-negative MC [108], with an equal frequency of
purpura (71% versus 75%) and renal involvement (34% versus 35%). Cacoub and colleagues
[109] noted five high prevalent extrahepatic manifestations in chronic HCV infection
including, arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca
syndrome (11%), and a 40% prevalence of cryoglobulins. These findings suggest the
possibility of an independent role of HCV infection in the clinicopathological manifestations
of MC and MCV. Among 114 patients including 18 children and 96 adults with
cryoglobulinemia between 2000 and 2012, children had more frequent prolonged fever (17%
versus 3%), petechiae and purpura (27% versus 15%), arthralgia and arthritis (66% versus
16%), and cutaneous involvement (77% versus 50%, than adults [110]. Aggressive optimal
therapy of HCV-related CV with PEGylated (PEG)-INF alpha to improve the pharmacologic
properties, and ribavirin with a protease inhibitor in the instance of HCV genotype 1
infection, should be considered as induction therapy for CV and administered for forty-eight
weeks for all HCV genotypes [108]. An induction phase of immunosuppression such as
rituximab plus antivirals is recommended in patients with more severe HCV-related CV
exemplified by worsening renal function, mononeuritis multiplex, extensive skin disease
including ulcers and distal necrosis [111].

Terrier and colleagues [107] showed a greater therapeutic efficacy of rituximab and
corticosteroids compared with corticosteroids alone and alkylating agents with corticosteroids
in achieving complete clinical, renal, and immunologic responses and a prednisone dosage of
< 10 mg per day at six months. However, this regimen was associated with severe infections,
particularly when high doses of corticosteroids were employed.

Plasmapheresis combined with immunosuppression can be useful in fulminant HCV-
related CV to engender an immediate effect but should be continued to avoid post-pheresis
rebound worsening. Rituximab, fludarabine, and cyclophosphamide treatment is effective
treatment for refractory CryoVas associated with lymphoma. One-year, 2-year, 5-year, 10-
year survival rates of 91%, 89%, 79% and 65% respectively, have been reported in patients
with CV [108] with fatalities related to serious infection and disease flares of CV.

Systemic Lupus Erythematosus

Although distinctly uncommon, two collagen-vascular disorders, SLE and RA can be
associated with vasculitis of the nervous system. The early concepts of the collagen-vascular
disorders introduced by Klemperer [112, 113] stemmed from the appreciation of fibrinoid
necrosis using collagen staining in patients with SLE. As collagen swells and fragments, it
dissolves to form a homogeneous hyaline and granular periodic acid-Schiff (PAS)-positive
material. The latter fibrinoid material contains immunoglobulins, antigen–antibody
complexes, complement, and fibrinogen. The organ-specific responses to this fibrinoid

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