Page 57 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 33

and cyclophosphamide, postmortem examination in four of whom failed to demonstrate
active vasculitis.

By comparison, seven patients (29%) died receiving other treatments, of which one so
studied at postmortem examination showed active vasculitis. Three forms of vasculitis
classically occur in RA affecting all calibers of blood vessels from dermal postcapillary
venules to the aorta, usually in association with circulating IgM and IgG rheumatoid factor as
measured by the latex fixation test, decreased complement levels, and a positive ANA. The
first is a proliferative endarteritis of a few organs, notably the heart, skeletal muscle, and
nerves characterized by inflammatory infiltration of all layers of small arteries and arterioles,
with intimal proliferation, necrosis, and thrombosis. The second is fulminant vasculitis
indistinguishable from PAN with less severe leukocytosis, myalgia, renal and gastrointestinal
involvement, and bowel perforation. The third type takes the form of palpable purpura,
arthritis, cryoglobulinemia, and low complement levels. The literature contains references to
RAV with involvement of the CNS at postmortem examination in only nine patients. Detailed
postmortem findings evidencing CNS vasculitis has been reported in only nine patients [134-
136, 138-142] with accompanying clinical neurological findings including, delirium,
confusion, seizures, hemiparesis, Gerstman-like syndrome, blindness, and peripheral
neuropathy. Postmortem examination has shown widespread systemic vasculitis, single major
cerebral artery involvement, generalized PAN-like changes in the CNS, isolated CNS
vasculitis affecting the temporal lobes and brainstem with diffuse infiltrative thickening of the
pia arachnoid, rheumatoid nodular formation, and inflammatory cell infiltration of
leptomeningeal vessels in subjacent brain tissue including the midbrain, medulla, and upper
cervical cord; and chronic perivasculitis and transmural chronic inflammatory cell infiltration
with severe fibrinoid necrosis of the media of small leptomeningeal vessels and cortical
arterioles.

Despite development of new and potent drugs for RA, there are no available
evidence-based recommendations for treatment of systemic rheumatoid vasculitis [143].
Complete remission of systemic rheumatoid vasculitis occurred in nearly three-fourths treated
with rituximab, with a significant decrease in daily prednisone dosage and an acceptable
toxicity profile, making it a suitable therapeutic option to induce remission but maintenance
therapy was necessary. Bartels and Bridges [144] recommended prednisone therapy to
initially decrease systemic inflammation with a dose dependent upon the degree of systemic
inflammation and level of organ system involvement. The presence of CNS involvement
mandated intravenous corticosteroid therapy and consideration of cytotoxic or biologic agents
from among them methotrexate, azathioprine, cyclophosphamide, anti-TNF agents and
rituximab. Bartolucci and colleagues [145] reported the successful induction of a prompt
symptomatic response in ten patients with systemic vasculitis not responsive to conventional
treatment, including two with RA and associated vasculitis. Puéchal and colleagues [146]
demonstrated evidence of efficacy of adjunctive anti-TNF therapy and corticosteroids for
treatment of active refractory systemic RAV with remission achieved in two-thirds of
patients, and a significant decrease in prednisone dose, with a higher risk of infection in the
most severely ill patients.

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