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with cytotoxic agents. Atherosclerosis is a potentially treatable comorbid factor that can
worsen prognosis. The Vasculitis Damage Index (VDI) [85] is a useful measure of the
cumulative impact of scars and sequela caused by the disease and its therapy.

Immunosuppressant Medication

The introduction of corticosteroids, which led to an improvement in the untreated 5-year
survival rate of 10% of the preceding two decades to 55% by mid-to-late 1970s [35, 47],
further increased to 82% by the addition of cyclophosphamide and azathioprine [47, 86].

Corticosteroids

Corticosteroids are administered for only a few days in those with HBV infection, but is
given as a prolonged course lasting up to one year in the presence of life-threating organ
involvement or the extension phase of mononeuritis multiplex, commencing with pulse
methylprednisolone dose of 7.5 to 15 mg/kg IV over 60 min, repeated at 24-h intervals for 1–
3 days. The side effects of an empiric dose of pulse-methylprednisolone dose <1000 mg are
usually mild and transient. However, severe side effects which are fortunately rare include
sudden death, cardiac arrhythmia, myocardial infarction, gastrointestinal bleeding, and
seizures. This is followed by prednisone in doses of 1 mg/kg/day or the equivalent dose of
methylprednisolone for two to three weeks after which tapering can begin. The FVSG trial
[87] which tapered the corticosteroid dose by one-half to 20 to 30 mg per day by three
months, aimed for a dose of 10 mg by six months, and 5 mg by one year. This gradual
reduction had the advantage of limiting side effects. The results of a prospective trial devoted
to treatment of vasculitides in the elderly noted that the dose of corticosteroids could be even
lower and still retain disease-free survival benefits.

Cyclophosphamide

Cyclophosphamide is administered in combination with corticosteroids at a dose of up to
2 mg/kg/day for three to six months, however it is associated with major side effects
including, hemorrhagic cystitis, bladder fibrosis, bone-marrow suppression, ovarian failure,
bladder cancer, and hematological malignancy [88]. In addition, life-threatening infection
can supervene when given in conjunction with high dose corticosteroids [60, 79]. Protocols
employing intermittent treatment with higher dose of cyclophosphamide to limit the
associated morbidity of daily doses were developed for the treatment of PAN [89].
Intravenous pulse cyclophosphamide is preferable to oral cyclophosphamide in the treatment
of systemic necrotizing vasculitis. The FVSG protocol employs a dose of 0.6 g/m2 given
every two weeks for three pulses, followed by a schedule of every three weeks for a total of
six treatments. Maintenance therapy with azathioprine or methotrexate, recommended in the
treatment of AAV [90, 91], is an acceptable yet invalidated approach in PAN.

It is the opinion of this author that cyclophosphamide should be given judiciously based
upon the anatomical location and severity of PAN involvement, rather than to all PAN

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