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NONSYSTEMIC OR ISOLATED PNS VASCULITIS
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In nearly 60% of all vasculitic neuropathies the vasculitis is restricted to peripheral nerves1,3,6,7,20,23,75 78 This socalled nonsystemic vasculitis or isolated PNS vasculitis is usually seen in adults, but children can also be affected6 The clinical, electrophysiological, and histopathological features of isolated PNS vasculitis are quite similar to PAN, except that there is no signi cant involvement of other organ systems Individuals who are affected may present with multiple mononeuropathies or a generalized symmetric sensorimotor polyneuropathy Laboratory testing may demonstrate elevated ESR or positive ANA titers Vasculitis may be apparent on muscle biopsies,5 but the peripheral nerves are predominantly affected The diagnostic yield of nding vasculitis is increased by biopsying both muscle and nerve The vasculitis typically involves small- and mediumsized arteries of the epineurium and perineurium, and immune complex deposition on these blood vessels may
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nausea Hydration is essential to minimize bladder toxicity Following intravenous pulses of cyclophosphamide, the leukocyte count drops The nadir of the leukopenia occurs between 7 and 18 days, during which time the risk of infection is greatest We check complete blood counts and urinalysis prior to each treatment Urinalysis is obtained every 3 6 months after treatment because of the risk of future bladder cancer If patients do not respond to pulsed cyclophosphamide, oral dosing should be tried prior to concluding that the patient failed cyclophosphamide treatment High-dose corticosteroids and cyclophosphamide are continued until the patient begins to improve or at least the de cit stabilizes This usually occurs within 4 6 months Subsequently, we discontinue the cyclophosphamide and start methotrexate (75 mg per week) The methotrexate dose is gradually increased as necessary Also at the same time we begin to taper the prednisone by 5 mg every 2 3 weeks The use of cyclophosphamide and glucocorticoids for induction and methotrexate for maintaining remission appears to be an effective and well-tolerated therapeutic regiment in patients with active Wegener s granulomatosis and is a reasonable approach in other vasculitic neuropathies84 Patients with CSS often require continued low doses of prednisone in order to control their asthma Relapses are uncommon in PAN, MPA, and isolated PNS vasculitis but occur in as many as 50% of cases of Wegener s granulomatosis2,41 Thus, life-long immunosuppressive therapy is required in many patients There is less experience with other immunotherapies in the treatment of vasculitis Methotrexate (015 03 mg/kg/week) in combination with corticosteroids can be effective in Wegener s granulomatosis44,84 Azathioprine, cyclosporine, tacrolimus, chlorambucil, and intravenous immunoglobulin have been tried in refractory cases with variable success81,85 87 PAN associated with hepatitis B or C infection deserves special comment Conventional treatment with high-dose corticosteroids and cyclophosphamide may allow the virus to persist and replicate, thus increasing the risk of liver failure Further, methotrexate can directly cause hepatotoxicity Some authorities advocate corticosteroids only for the rst few weeks of treatment to manage life-threatening manifestations of systemic vasculitis and then switch over to maintenance therapy with plasma exchange and antiviral agents such as vidarabine or -interferon2 The 7-year survival rate using this regimen in patients with hepatitis B-related PAN was 83%, while the HBeAG/HBeAB conversion rate was 51%, and total viral clearance was seen in 24% all of which represent a signi cant improvement from that seen with corticosteroids with or without cyclophosphamide or plasma exchange88 In patients with mixed cryoglobulinemia, due to hepatitis C infection, treatment with -interferon
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(3 million units three times a week) may be effective12,56,70,89 94 As in PAN associated with hepatitis B or C, a short course of corticosteroids may be required to control the initial manifestations of the systemic vasculitis followed by plasma exchange and -interferon Small series suggest that rituximab may be bene cial in cryoglobulinemic vasculitis, although it probably should not be used in cases related to hepatitis infection95,96
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