• Safety of Rituximab in patients with Churg-Strauss [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  
• Remission of renal disease activity as indicated by stable or falling creatinine, absence of active urinary sediment AND reduction of oral prednisone dose to less than 50% of average dose of preceding 3 months or less than 10 mg/day (whichever smaller) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  

• Normalization of eosinophil count at six months. Normalization is defined as total eosinophil counts <1.5 x 109/l. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  

Drug: Rituximab
Patients will receive 4 weekly doses of rituximab 375 mg/m2. Patients will also receive prednisone with progressive tapering aiming to discontinuation at 6 month.

Many patients do not respond satisfactorily to glucocorticoid monotherapy. Current recommendations are to use glucocorticoids in combination with cyclophosphamide, which is associated with increased toxicity. In addition, resistance to glucocorticoid therapy occurs and some patients cannot be tapered off glucocorticoids ± cyclophosphamide without prompt relapse. Approximately 70% of patients are ANCA positive suggesting that ANCA may have a pathogenic role in this disease. Rituximab has been effective in the treatment of a number of autoimmune diseases including ANCA associated vasculitis and SLE. Approximately 10% of patients with ANCA-associated vasculitis are refractory to the standard therapy of corticosteroids and cyclophosphamide or suffer severe dose-limiting side effects. Since 1999 we have treated over 30 patients with ANCA vasculitis in whom cyclophosphamide was ineffective at maximally tolerated doses or was contraindicated (cytopenia, hemorrhagic cystitis). Patients were treated with a combination of Rituximab (375 mg/m2 weekly x 4) and high-dose corticosteroids (followed by a steroid taper) between. Following Rituximab infusion, circulating B cells became undetectable and ANCA titers decreased significantly in all. Alveolar hemorrhage resolved in all and renal function was improved. Remission was achieved in all and corticosteroids were successfully tapered in all. Remission was maintained in all while B-cells were undetectable. Patients who relapsed in the presence of normal B-cell counts and rising ANCA-titer rise were successfully retreated. No serious adverse events attributable to Rituximab were observed. (41, 42) We are now conducting a multicenter, randomized, double blind, double placebo controlled trial testing standard therapy (prednisone + cyclophosphamide) versus prednisone + Rituximab for the induction of remission and tolerance in ANCA-associated vasculitis (RAVE), which is sponsored by the Immune Tolerance Network and the NIH (ITN021A1). Enrollment was started in 03/05. Finally, B lymphocyte depletion has also been successful in treating other autoimmune diseases, which until recently were thought to be predominantly T lymphocyte-mediated, such as rheumatoid arthritis.

Inclusion Criteria:

1. Patients with Churg-Strauss syndrome as defined by meeting one of 3 sets of criteria for Churg-Strauss Syndrome described above who have not yet been treated, who have failed steroid therapy (partial or non-responders) or who can not been tapered off oral prednisone because of documented relapsing disease.
2. Renal involvement (>25% dysmorphic red cell, rbc casts, or pauci-immune GN on biopsy)
3. Age >18 years old.
4. Serum creatinine &#61603; 3.0mg/dl.
5. Able and willing to give written informed consent and comply with the requirements of the study protocol.
6. Negative serum pregnancy test (for women of child bearing age).
7. Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.