Anti-T-cell-directed treatment with ATG may be a therapeutic option for severe refractory Wegener's granulomatosis if simultaneous infections and fluid overload have been ruled out. In patients with alveolar hemorrhage, ATG should only be used under special caution.

ABSTRACT. The combination of cyclophosphamide (CYC) and oral corticosteroids is effective in the majority of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AASV), but it carries substantial risk of drug-related morbidity and mortality. New regimens are desired, especially in refractory cases. The immunosuppressant 15-deoxyspergualin (DSG) is effective in experimental autoimmune disease and transplantation as well as in acute kidney transplant rejection in humans. To assess the efficacy and safety of DSG, an open label multicenter trial was conducted in patients with AASV who were either unresponsive or had contraindications for standard immunosuppressants. Included were 19 cases of Wegener granulomatosis and one case of microscopic polyangiitis. Nine of them had received CYC shortly before study entry without apparent therapeutic success. DSG (0.5 mg/kg per d) was given for 2 to 3 wk until the WBC count dropped to 3000/μl followed by a rest until at least a WBC of 4000/μl was reached again. This was repeated up to six cycles. During the study, no other immunosuppressants besides steroids were allowed. Disease improvement during treatment with DSG was achieved in 70% of cases (six cases of complete remission; eight cases of partial remission). Leucopenia occurred in each patient in a regular pattern during the cycles and was transient without exception. No mortality or septicemia was observed. Mild to moderate infections mainly in the respiratory tract were observed but resolved under adequate treatment without sequel. It is concluded that treatment with DSG is successful in patients with refractory Wegener granulomatosis under careful monitoring of WBC count. E-mail: rainer.birck@med5.ma.uni-heidelberg.de

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SUMMARY:Aim: To survey the evidence for plant-products to modify cytochrome P450 enzyme, and transport protein mediated drug metabolism in renal transplant patients. Methods: A literature search was performed to identify "in vitro" and "in vivo" research on plant-products that might cause overdosage or loss of efficacy of immunosuppressive drugs in transplant patients by the interaction mechanisms already characterized for grapefruit juice and St. John's Wort. Results: The interaction mechanisms of St. John's Wort by pregnane X-receptor mediated upregulation of cytochrome-P450 enzyme 3A4 and p-glycoprotein expression and of grapefruit juice by mechanism-based inhibition of intestinal CYP3A4 suggest that many other plant products will likewise cause interactions with drugs because they occupy the same metabolic pathways. The respective research on foods, spices and medicinal herbs is listed in a comprehensive table and weighted according to its strength of evidence to cause clinically relevant interactions. Conclusion: Physicians supervising drug-regimes in renal transplant patients should be aware of plant products beyond SJW and GFJ to possibly cause overdosage or failure of drug-treatments by herb-drug interactions.

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