Fifteen patients with Wegener's granulomatosis, polyarteritis nodosa, or isolated angiitis of the central nervous system were treated with cyclophosphamide according to a widely used regimen. Seventeen clinical episodes of infection were observed over 201 patientmonths of cyclophosphamide therapy, and 2 patients died of pneumonia. Notably, neither the incidence of leukopenia nor the dosage or duration of cyclophosphamide or corticosteroid therapy correlated well with infection, which occurred most frequently in men over 60 years of age. Patients with Wegener's granulomatosis appeared to be at greater risk of infection than those with the other forms of vasculitis. These results suggest that this treatment regimen may not be as safe as was previously thought.
The use of cyclophosphamide in the treatment of certain vasculitis syndromes has resulted in a dramatic improvement in patient outcome (1,2). Patients with Wegener's granulomatosis (WG) (3-7), systemic necrotizing vasculitis (8-lo), and isolated angiitis of the central nervous system (CNS angiitis) ( I 1) have shown high response rates, with modest treatment toxicity and few treatment-related deaths.
Treatment guidelines for the use of cyclophosphamide in WG (1-5) were published more than a decade ago. These guidelines optimize the response of the vasculitis and minimize the risk of adverse effects, and are still accepted by most practicing rheumatologists. This regimen has also been successfully used in the treatment of other vasculitides, including systemic necrotizing vasculitis and CNS angiitis (1,2,8-1 I).
Usually, cyclophosphamide is administered orally in an initial daily dose of 1-2 mg/kg. The daily dose is then increased by 25 mg every 2 weeks until a clinical response is evident or serious toxic effects, such as leukopenia (<3,000/mm3) or neutropenia (< 1,000-1 ,500/mm3), develop (1-5). The maintenance dose is adjusted to maintain the clinical response and adequate leukocyte counts (1-5). and cyclophosphamide is generally continued for I year after complete remission of the vasculitis (2,5). The daily dose is then reduced by 25 mg every 2-3 months while the patient is observed for recurrence of the vasculitis.
Corticosteroids are also an integral component of the treatment of WG, systemic necrotizing vasculitis, and CNS angiitis. In addition to their antiinflammatory effects, data suggest that they may provide protection from the myelosuppressive effects of cyclophosphamide (23). Recommendations for the corticosteroid From the Rheumatology Division, Department of Internal component of the treatment of vasculitis have changed Medicine,