Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
Eur J Med Res (2009) 14(Suppl. IV): 265-267
© I. Holzapfel Publishers 2009
CO-TRIMOXAZOLE AND PREVENTION OF RELAPSES OF PR3-ANCA POSITIVE VASCULITIS WITH PULMONARY INVOLVEMENT K. Zycinska, K. A. Wardyn, T. M. Zielonka, R. Krupa, W. Lukas
Primary Systemic Vasculitis Outpatient Clinic, Department of Family Medicine, Internal and Metabolic Diseases, Warsaw Medical University, Warsaw, Poland
Abstract Background: Bacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis. Data have suggested that treatment with co-trimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus. Goal and methods: Prospective, randomized, placebocontrolled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener’s granulomatosis (WG) in remission, after treatment with cyclophosphamide and prednisolone was conducted. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, serological, microbiological, and histopathological findings. Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo. Results: Seventy five percent of the patients in the cotrimoxazole group remained in remission at 18 months and 55% of those in the placebo group. A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment, chronic nasal crusting, and Staphylococus aureus infection as risk factors for relapse. Furthermore, the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged diseasefree interval. Conclusion: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener’s granulomatosis in remission. Key words: co-tromoxazole, relapse, Wegener’s granulomatosis
INTRODUCTION
Wegener’s granulomatosis (WG) is an autoimmune disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract and necrotizing crescent glomerulonephritis. The pathogenesis of the disease is not well known. Patient with WG frequently have clinical symptoms of respiratory tract infection and the ANCA titer elevation [1]. Furthermore, they have frequent secondary infections of the nasal and paranasal tissue caused by Staphyloccocus aureus [2, 3]. A possible role for bacteria and viruses in recurrent Wegener’s granulomatosis is suggested by studies of beneficial effects of co-trimoxazole [4, 5]. Trimetoprim and sulfamethoxazole (co-trimoxazole) inhibit
bacterial synthesis of tetrahydrofolic acid, the physiologically active form of folic acid and co-factor in thymidine synthesis; thus bacterial DNA. Thrimetoprim-sulfametoxazol is available in oral and intravenous preparations. The standard single-strength tablet contains 80 mg of trimetoprim and 400 mg of sulfametoxazole, and the more clinically used doublestrength tablet contains
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