Summary
Considering cyclophosphamide's severe side effects there is a need for a new, less toxic treatment protocol for Wegener's granulomatosis. Here we report the first results of a prospective study using cyclophosphamide pulse therapy (monthly application) (a) as an alternative treatment in seven cases of active generalized Wegener's granulomatosis, which either showed complications under continuous cyclophosphamide treatment or in which the partial remission was not steady, and (b) as the initial treatment in five newly diagnosed patients with active generalized disease. After complete remission had been achieved in all cases in group (a), but only two cases in group (b), we started treatment with trimethoprim/sulfamethoxazole (cotrimoxazole) to maintain remission. Three of 8 patients suffered from severe relapses 9, 11 and 12 months after discontinuation of cyclophosphamide. The 3 patients in group (b) who could not be brought into remission had to be put on continuous cyclophosphamide. In addition, we treated 3 patients with newly diagnosed locoregional disease with cotrimoxazole alone. Two of these patients responded promptly and have only minor symptoms after 13 and 27 months, respectively. In one patient the disease continued to progress in the upper respiratory tract, and treatment was switched to cyclophosphamide and prednisolone after a period of 3 months. From these results we believe that cyclophosphamide pulse therapy is a successful alternative treatment protocol after partial remission has been achieved with a daily administration of cyclophosphamide or if complications, e.g-. leukopenia, arise with the continuous use of this drug.
As an initial treatment, however, bolus treatment still appears to be an experimental protocol. Our experience with cotrimoxazole for maintaining remission has not left us particularly confident, though in the initial phase of the disease this drug might be worth trying.
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Abbreviations
- WG:
-
Wegener's granulomatosis
- CYC:
-
cyclophosphamide
- T/S:
-
trimethoprim/sulfamethoxazole
- E:
-
upper respiratory tract
- L:
-
lung
- K:
-
kidney (ELK classification)
- ACPA:
-
antibody against intracellular antigens in neutrophilic leucocytes
References
Andrassy K, Koderisch J, Rasmussen N, Ritz E (1989) Therapie der Wegener'schen Granulomatose und verwandter Vaskulitiden. Dtsch med Wochenschr 114:27–29
Austin HA, Klippel JH, Balow JE (1986) Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Eng J Med 314:614–418
Colburn KK, Cao JD, Krick EH, Mortensen SE, Wong LG (1985) Hodgkin's lymphoma in a patient treated for Wegener's granulomatosis with cyclophosphamide and azathioprine. J Rheum 12/3:601–602
DeRemee RA, McDonald TJ, Harrison EG Jr, Coles DT (1976) Wegener's granulomatosis: anatomic correlates, a proposed classification. May Clin Proc 51:777–781
De Remee RA, McDonald TJ, Weiland LH (1985) Wegener's granulomatosis: observation on treatment with antimicrobial agents. Mayo Clin Proc 60:27–32
DeRemee RA (1988) The treatment of Wegener's granulomatosis with trimethoprim-sulfamethoxazole: illusion or vision? Arthritis Rheum 31:1068–1072
Fauci AS, Haynes BF, Katz P, Wolff SM (1983) Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76–85
Gross WL, Lüdemann J, Lüdemann G (1987) Wegener'sche Granulomatose: Klinisch-immunologische Aspekte. Med Welt 38:452–456
Gross WL (1989) Wegener's granulomatosis — new aspects of the disease course, immunodiagnostic procedures and stage-adapted treatment. Sarcoidosis 6:15–29
Leavitt RY, Hoffman GS, Fauci AS (1988) Response: role of trimethoprim/sulfamethoxazole in the treatment of Wegener's granulomatosis. Arthritis Rheum 31:1073–1075
Lüdemann G, Nölle B, Rautmann A, Roosenboom S, Kekow J, Gross WL (1988) Antizytoplasmatische Antikörper als Seromarker und Aktivitätsparameter der Wegener'schen Granulomatose. Dtsch med Wochenschr 113:413–417
Nölle B, Specks U, Lüdemann J, Rohrbach MS, DeRemee RA, Gross WL (1989) The immunodiagnostic value of antineutrophil cytoplasmic autoantibodies. Ann Intern Med (in press)
Santa GR, Ucci AA Jr. Meares EM (1983) Renal immunoblastic sarcoma complicating immunosuppressive therapy of Wegener's granulomatosis. Urology 11/6:632–634
Scott DGI, Salmon M, Bacon PA (1987) Pulsed cyclophosphamide (CY) and steroids in systemic vasculitis. Clin rheumatol 6:132
Steinberg AD (1984) Cyclophosphamide: should it be used daily, monthly or never? N Engl J Med 16:458–459
Steppat D, Parpatt PM, Gross WL (1988) Erste Ergebnisse einer prospektive Studie zur stadienadaptierten Therapie bei der Wegener'schen Granulomatose. Z Rheumatol 47:259
Stillwell TJ, Benson RC Jr, DeRemee RA, McDonald TJ, Weiland LH (1988) Cyclophosphamide-induced bladder toxicity in Wegener's granulomatosis. Arthritis Rheum 31:465–466
Weiner SR, van Nuys, Paulus HE (1986) Treatment of Wegener's granulomatosis with cyclophosphamide, an outcome analysis. Am Rheum Assoc: Scientific Abstracts 14W
Wheeler GE (1981) Cyclophosphamide-associated leukemia in Wegener's granulomatosis. Ann Intern Med 94:361
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Supported by the Bundesministerium für Forschung und Technologie (01 VM 86224), the “Verein zur Förderung der Forschung und Bekämpfung rheumatischer Erkrankungen e.V.” Bad Bramstedt and the Hermann and Lilly Schilling-Stiftung
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Steppat, D., Gross, W.L. Stage-adapted treatment of Wegener's granulomatosis. Klin Wochenschr 67, 666–671 (1989). https://doi.org/10.1007/BF01718027
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DOI: https://doi.org/10.1007/BF01718027