Page 56 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

32 David S. Younger

increased risk of severe ExRA manifestations. Major cutaneous vasculitis and vasculitis
involving other organs are two such ExRA occurrences.

The diagnosis of RAV has generally been ascertained according to the criteria of Scott
and Bacon [129] according to the presence of one or more of the following: 1) mononeuritis
multiplex; 2) peripheral gangrene; 3) biopsy evidence of acute necrotizing arteritis plus fever
and weight loss; and 4) deep cutaneous ulcers or active ExRA disease if associated with
typical digital infarcts or biopsy evidence of vasculitis. Watts and colleagues [130] reported
an annual incidence of RAV of 11.6 per million inhabitants between 1988 and 1992 in the
Norfolk area of the United Kingdom, and a rate of 3.6 per million between 1998 and 2002.
Myasoedova and coworkers [131] reported a ten-year cumulative incidence of 50% of any
ExRA, including cutaneous and other organ-specific RAV in a retrospective population-based
cohort study of 463 RA patients in Olmsted County, Minnesota from 1995 to 2007. The ten-
year cumulative incidence of RAV, but not other ExRA, was significantly lower in the 1995-
2007 cohort (0.6%) compared to the 1985 to 1994 cohort (3.6%). The markers of RA severity
including RA positivity, erosion and joint destructive changes (21% among those in the 1985
to 1994 cohort, compared to 29% in 1995 to 2007), use of methotrexate, other disease-
modifying anti-rheumatic drugs, and systemic corticosteroids were significantly associated
with ExRA development between 1995 and 2007. Vollerstein and colleagues [132] studied 52
patients with RAV at the Mayo Clinic from 1974 to 1981, who developed clinical vasculitis
evidenced by classic ischemic skin lesions, mononeuritis multiplex, or a positive tissue
biopsy in comparison to population controls. The initial manifestation of vasculitis was seen
in skin (26 patients), nerve (20 patients) or both (3 patients), and mononeuritis multiplex
presented in one (2 patients), two (9 patients), three (5 patients) or four nerves (4 patients).
More than 90% of tissue biopsy specimens revealed vascular necrosis and inflammation.
At diagnosis, 80% of patients began therapy with aspirin and other non-steroidal anti-
inflammatory drugs however three-fourths continued or began corticosteroid therapy. Sixteen
of the original 52 patients eventually received cytotoxic immunosuppressive therapy.
Compared to the general population, those with RAV had decreased survival that was
immediately evident and continued for six years. Compared with a previously reported
incidence cohort [133] and adjusted for referral bias, survival of RAV was not different from
classic RA. The factors that predicted decreased survival in RAV in a univariate proportional-
HR model included older age, failure to receive previous non-steroidal anti-inflammatory
drugs, previous administration of cytotoxic immunosuppressive agents, a higher dose of
corticosteroids at diagnosis, decision to continue or initiate corticosteroids, and abnormal
urinary sediment. Ouyang and coworkers [134] estimated CNS involvement in RA to be
extremely uncommon, and other authors [135, 136] found CNS vasculitis to be decidedly
rare. Puéchal and colleagues [137] found vasculitic involvement of vasa nervorum of both
small- and medium-sized arteries indistinguishable from PAN in 64% of patients, with a
mortality ranging from 28 to 44% according to the length of follow-up. Epineurial and
perineurial vasculitis was observed with the same frequency among those with primary
sensory neuropathy as others with predominant motor involvement, respectively 67% versus
64%. A greater extent of the neuropathy and motor involvement tended to predict decreased
survival, however mononeuritis multiplex was not associated with a poor five-year survival
rate (57%) than was distal symmetrical sensory or sensorimotor neuropathy (55%). Scott and
Bacon [129] reported that five patients (24%) died in the group receiving methylprednisolone

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