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Wegener’s granulomatosis is characterized by the formation of necrotizing granulomas in
the vicinity of affected inflamed vessels. The target organs are the nasal mucosa, paranasal
sinuses, respiratory tract, pulmonary parenchyma.
Patients may present with
pansinusitis, recurrent pneumonia, or renal disease that is marked by hematuria, pyuria, and
azotemia. Nonspecific features of this disorder include fever, polyarthralgias, and
polyarthritis. Necrotic skin nodules may also occur. The diagnosis is suggested by the
clinical features and radiologic changes in the paranasal sinuses and pulmonary tissue
and is confirmed by
Testing for c-ANCA has a high degree of specificity and sensitivity for
Wegener’s granulomatosis. Other forms of vasculitis are virtually the only source of false
positive results. How this test is performed is crucial; experience is needed to interpret
indirect immunofluorescent assays. Enzyme-linked immunosorbent assays using highly
purified antigen are available.
In untreated Wegener’s granulomatosis, death, usually from renal disease, occurs
commonly within weeks or months after the onset of the disorder. Therapeutic advances,
however, have improved the outlook significantly. Corticosteroids lengthen the mean survival
time by a few months. Cyclophosphamide achieves an even better response and is the
treatment of choice. In patients with a relatively stable course (i.e., abnormal renal function
but no fulminant renal failure), oral cyclophosphamide (1 to 2 mg/kg/day) is given and
maintained for two weeks. If treatment is successful, the dosage is then adjusted to maintain
the total leukocyte count above 3,000/mm3. If there is no favorable response, the dose
should be increased by 25 mg every two weeks until a beneficial response or leukopenia
occurs. In patients with life-threatening disease, intravenous cyclophosphamide (4
mg/kg/day) is given for three days, followed by the regimen outlined above. A daily
high-dose regimen of prednisone (60 mg) is added for those patients with severe disease and
tapered to an alternate-day dosage within a few weeks. Thereafter, the corticosteroid may be
stopped and the patient maintained on the cytotoxic agent alone. In many patients, the disease remits,
allowing cessation of therapy within 12 to 18 months.
So-called pulse cyclophosphamide therapy is another alternative form of therapy in aggressive disease. It has also been demonstrated that
trimethoprim-sulfamethoxazole is useful in the management
of Wegener’s granulomatosis that is limited to a few organ systems and is of
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