Page 244 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

218 Loic Guillevin

patients. Oral low-dose cyclophosphamide was successfully employed to control disease
activity and relapses within the first six months of treatment in patients with systemic
vasculitis who failed to respond to pulse intravenous high-dose regimen [92]. Patients with
PAN and associated poor-prognostic factors should be treated with combination
corticosteroids and cyclophosphamide for six months, followed by a corticosteroid agent and
less toxic immunosuppressant such as azathioprine or methotrexate. Patients without such
poor prognostic factors can be treated safely with corticosteroids alone and adjuvant
immunosuppression introduced only in cases of treatment failure for disease control [93].

Other Cytotoxic Agents

Azathioprine, methotrexate and other cytotoxic agents are reserved for patients with
contraindications to the initial or continued use of cyclophosphamide, and as maintenance
therapy for up to eighteen months.

Plasma Exchange

There is little support for the use of plasma exchange in PAN in the absence of HBV
infection [94], including those with poor-prognosis factors [95]. However plasma exchange
could conceivably be considered as a second-line treatment of PAN refractory to conventional
therapy and to limit renal disease sequela of patients with AAV.

Rituximab

At present, this is not suitable pathogenic mechanism, published finding, or ongoing
study of the use of rituximab in the treatment of PAN.

HBV-Related PAN

Patients treated with conventional regimens of corticosteroids and cyclophosphamide
allows the HBV to replicate, facilitating the development of chronic hepatitis and liver
cirrhosis. Instead, the preferred initial treatment approach is plasma exchanges combined with
vidarabine or interferon-?2b, and corticosteroids to rapidly control the most severe life-
threatening manifestations of PAN commonest during the first few weeks of disease.
Afterward, the corticosteroid agent can then be safely and abruptly discontinued to enhance
immunological clearance of HBV-infected hepatocytes, favoring anti-HBeAb seroconversion.
This strategy [96, 97] which is preferred over conventional regimens, was confirmed among
41 patients, 23 (56.1%) of whom no longer exhibited serological evidence of replication, and
an overall cure rate of 80.5% [98]. The antiviral agent lamivudine [3], which increases the
seroconversion rate from 56.1% to 60%, did not confer additional improvement in the
survival rate at 18 months. Those treated with conventional corticosteroids with or without
cyclophosphamide and no antiviral drugs demonstrated a mortality rate of 27.5% at 18

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