An Open Trial of the Efficacy of Glucocorticoids and Methotrexate (MTX) in the Treatment of Systemic Vasculitis

Inclusion Criteria

INCLUSION CRITERIA:

Diagnosis: Wegener's granulomatosis.

Age: 10-80 years.

Qualifications to eligibility:

Prior documentation of vasculitis based on clinical characteristics and histopathological
and/or angiographic evidence of vasculitis. Patients will be eligible for this study
regardless of whether they are currently receiving immunosuppressive therapies. Failure
to respond to prior therapy with other cytotoxic agents or toxicity from such agents, in
the setting of persistent disease, will constitute one reason for eligibility for this
study.

In the absence of histopathological and/or angiographic evidence of vasculitis, patients
with the following criteria will also be eligible:

A. Positive C-ANCA (done at the NIH), and

B. Glomerulonephritis as evidenced by the presence of red blood cell casts and proteinuria
or renal biopsy showing necrotizing glomerulonephritis in the absence of positive
immunofluorescence for immunoglobulin and complement, and

C. One or more of the following:

Inflammatory sinusitis with histopathological evidence of granulomatous inflammation and
negative special stains for mycobacteria and fungi. Sinusitis must be present for at
least 3 months and have failed to respond to at least 2 weeks of antibiotic therapy
directed against likely pathogens (H. influenza, S. pneumonia, and upper respiratory tract
anaerobic bacteria);

Pulmonary nodule or infiltrates in a patient in the absence of infection.

Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater
than or equal to 3 (Appendix I) or if begun on immunosuppressive therapy at an outside
institution, a history of a Vasculitis Disease Activity Index greater than or equal to 3
during the past 6 months.

EXCLUSION CRITERIA:

Evidence of infection by gram stain and/or culture specimens. In those instances in which
infection cannot be ruled out by gram stain and culture of secretions or collections of
fluid in involved organs, it may be necessary to obtain a biopsy of the affected tissue
for microbiological and histopathological studies.

Recent (within four weeks) increase in GC or cytotoxic drug therapy.

Patients who are pregnant or nursing infants will not be eligible. Fertile women should
have a negative pregnancy test within one week prior to study entry and should be using
effective means of birth control.

Processes that would predispose to enhanced risk of MTX toxicity: acute or chronic liver
disease, alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week),
active peptic ulcer disease, and inability to comply with study guidelines.

Serological evidence of infection with human immunodeficiency virus (a serological
determination will be performed within two weeks of study entry).