Page 331 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Rheumatoid Arthritis Vasculitis 305

intravenous cyclophosphamide plus intravenous methylprednisolone were more likely to
experience healing and significant improvement in nail infarcts, leg ulcers, sensory
neuropathy, and mononeuritis than those receiving other medications [9]. Patients receiving
intravenous cyclophosphamide plus intravenous methylprednisolone were also less likely to
have relapses of their RV or to suffer serious complications such as limb amputation or death.
Patients receiving intravenous cyclophosphamide plus intravenous methylprednisolone did
better than those receiving the other medications despite having more serious disease at
baseline. In a case series of 16 RA patients with necrotizing scleritis or peripheral ulcerative
keratitis refractory to aggressive therapy with topical and systemic steroids and NSAID, 8
(50%) patients ultimately responded to cyclophosphamide, 6 (38%) eventually responded to
methotrexate, and 1 (6%) patient eventually responded to cyclosporine A [31]. In addition to
medical therapy, 9 (56%) patients with peripheral ulcerative keratitis also required surgical
therapy, including ulcer debridement, conjunctival resection, application of cyanoacrylate
tissue adhesive, and tarsorrhaphy. Abel and colleagues [41] reported a series of 5 patients
with RV who clinically improved following treatment with oral cyclophosphamide. There
were patients in whom cyclophosphamide was ineffective and those with contraindications to
this particular therapy. In such instances, treatment with other medications, such as tumor
necrosis factor (TNF) inhibitors [36, 42] and rituximab [43, 44], has been attempted.
However, evidence to date is limited to case reports and case series.

Tumor Necrosis Factor Inhibitors

Unger and colleagues [42] reported three patients with RV who developed treatment-
limiting adverse effects or a poor clinical response to cyclophosphamide and a later beneficial
response to infliximab. Puéchal and colleagues [36] performed a retrospective study of nine
patients with RV treated with etanercept or infliximab after failing to respond to treatment
with a mean cumulative dose of 8.4 g (range 4 to 15 g) of cyclophosphamide over a mean of
6.2 months (range 3 to 10 months) and high dose corticosteroids. Of the nine patients, five
developed a complete remission and experienced partial remission after a mean of 28.6 weeks
of therapy. Two patients withdrew due to adverse effects and one patient never achieved
remission. Two of the patients who responded to TNF inhibitory therapy developed four
cutaneous relapses. In two patients with RV studied in an open-label pilot study of infliximab
[45], both of whom were previously refractory to cyclophosphamide, one patient
demonstrated complete responsiveness to infliximab and the other a partial response. Garcia-
Porrua and Gonzalez-Gay [46] reported a patient with refractory RV-associated MNM and
sural nerve biopsy tissue specimen that revealed necrotizing vasculitis with fibrinoid necrosis
in whom foot drop improved after treatment with methotrexate and infliximab. Van der Bijl
and colleagues [47] described a patient with RV characterized by fibular mononeuropathy in
who foot drop improved following the addition of infliximab to the regimen of methotrexate.

Rituximab

A retrospective study of 17 patients with RV from the Autoimmunity and Rituximab
Registry [48] reported that 12 (71%) patients achieved a complete response and 4 (23%)

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