Re: antimicrobic treatment of Wegeners granulomatosis in the 80s and 90s

[Guest guest]

This is a good result, but I'm surprised the study takes such a conservative approach to its analysis...eg. "...The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity..." Why even go there with the immunsuppression stuff? Reading the following at a site on Wegener's... "...Rhinorrhea can result from nasal inflammation or sinus drainage and can cause pain. A hole may develop in the cartilage of the nose, which may lead to collapse (called saddle-nose deformity). The eustachian tubes, which are important for normal ear function, may become blocked, causing chronic ear problems and hearing loss.

Bacterial infection can cause Wegener's-related sinusitis (inflammation of the sinuses) with congestion and chronic sinus pain. http://www.niaid.nih.gov/factsheets/wegeners.htm ...makes me wonder how the heck they think a "hole may develop in the cartilage" if there's no bone eating bacteria involved? Geez, sounds an awful lot like what I've been going through. penny <usenethod@...> wrote: ========================Mayo Clin Proc. 1985 Jan;60(1):27-32. Related Articles, Links Wegener's granulomatosis: observations on treatment with antimicrobial agents.DeRemee RA, Mc TJ, Weiland LH.Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.Publication Types: Case ReportsPMID: 3871238 [PubMed - indexed for MEDLINE]

======================Arch Otolaryngol Head Neck Surg. 1989 Apr;115(4):515-8. Links Three cases of Wegener's granulomatosis treated with an antimicrobial agent.Fukuda K, Yuasa K, Uchizono A, Matsuyama H, Shimada K, Ohyama M. Department of Otolaryngology, Kagoshima (Japan) University School of Medicine.Sulfamethoxazole-trimethoprim, an antimicrobial agent, was used to treat three cases of cytotoxic agent-resistant Wegener's granulomatosis; one case was refractory to a regimen consisting of azathioprine and prednisolone, and in another two cases the therapy was insufficient to control the disease. By the introduction of sulfamethoxazole-trimethoprim, which has an advantage of fewer side effects compared with the conventional agents, into the regimen, the disease condition was markedly improved in all cases within four months. Sulfamethoxazole-trimethoprim is thus

considered as one of the most promising drugs to treat, especially, cytotoxic agent-resistant Wegener's granulomatosis. The possible underlying mechanism of the effect of sulfamethoxazole-trimethoprim is also described.PMID: 2784319 [PubMed - indexed for MEDLINE]===========================Arthritis Rheum. 1988 Aug;31(8):1068-74. Related Articles, Links The treatment of Wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision?DeRemee RA.Division of Thoracic Disease and Internal Medicine, Mayo Medical School, Rochester, Minnesota.Publication Types: Biography Historical Article Personal Name as Subject: Wegener FPMID: 3044373 [PubMed - indexed for MEDLINE] =======================================Ann Intern Med. 1987 Jun;106(6):840-2. Links Wegener granulomatosis and

trimethoprim-sulfamethoxazole. Complete remission after a twenty-year course.West BC, Todd JR, King JW. Wegener granulomatosis was diagnosed in a 42-year-old woman in 1965. Although a regimen of azathioprine and prednisone was helpful, the disease progressed. Cyclophosphamide was added to this regimen in 1969. On three separate occasions her disease relapsed when cyclophosphamide therapy was discontinued. In 1984, she developed cyclophosphamide-resistant disease and drug toxicity. We were able to discontinue cyclophosphamide therapy after a trimethoprim-sulfamethoxazole regimen that was begun in February 1985 led to rapid improvement, a fall in the erythrocyte sedimentation rate, and a complete remission. Her 22-year survival is the longest one reported. Because patients with Wegener granulomatosis sometimes respond to trimethoprim-sulfamethoxazole, this therapy deserves careful study and

implies that Wegener granulomatosis is an as yet unidentified infection.PMID: 3495214 [PubMed - indexed for MEDLINE]==============================Arch Intern Med. 1988 Oct;148(10):2293-5. Links Sulfamethoxazole-trimethoprim therapy for Wegener's granulomatosis.Israel HL.Department of Medicine, Jefferson Medical College, Jefferson University, Philadelphia, PA 19107.Cyclophosphamide has proved to be the most effective therapy for Wegener's granulomatosis, but mortality remains high at many medical centers, and the necessity for giving this toxic agent for many years to prevent relapses remains a major problem. Successful treatment of this disease with sulfamethoxazole-trimethoprim has been reported by DeRemee et al, and experience in a series of ten patients at Jefferson University Hospital, Philadelphia, confirms its effectiveness. Nine patients are in

remission, and the condition of one patient improved. Relapses occurred in four patients after intervals of remission ranging from four to 30 months, but responded to increased doses of trimethoprim in two patients, while two patients required resumption of therapy with cytotoxic agents. Although the effects of sulfamethoxazole-trimethoprim are suppressive rather than curative, its use represents a major advance in treatment of Wegener's granulomatosis, permitting successful treatment of many patients without high toxic doses of cyclophosphamide and prednisone.PMID: 3263099 [PubMed - indexed for MEDLINE]==================================Arch Intern Med. 1991 Aug;151(8):1649-52. Links Treatment of Wegener's granulomatosis with sulfamethoxazole-trimethoprim.Valeriano-Marcet J, Spiera H. Division of Rheumatology, Mount Sinai Medical Center, New York, NY

10029.Sulfamethoxazole-trimethoprim may be an alternative or adjunctive treatment for Wegener's granulomatosis, as suggested by our experience with six patients. Two had limited Wegener's granulomatosis; one of these achieved remission with sulfamethoxazole-trimethoprim alone, and the second achieved remission with sulfamethoxazole-trimethoprim and prednisone. Four patients presented with sinus, pulmonary, and renal involvement. One patient initially treated with sulfamethoxazole-trimethoprim developed worsening renal function requiring cytotoxic therapy. Two patients initially treated with cytotoxic agents achieved remission coincident with the addition of sulfamethoxazole-trimethoprim for persistent sinus symptoms. One patient had relapse of pulmonary symptoms after achieving and maintaining a remission during treatment with sulfamethoxazole-trimethoprim alone. This experience

suggests that sulfamethoxazole-trimethoprim may be an effective treatment for some patients with Wegener's granulomatosis and may be the only agent required. Patients require careful follow-up and still may need cytotoxic therapy.PMID: 1872670 [PubMed - indexed for MEDLINE]===============================N Engl J Med. 1996 Jul 4;335(1):16-20. Links Comment in: ACP J Club. 1996 Nov-Dec;125(3):67. N Engl J Med. 1996 Dec 5;335(23):1769-70. N Engl J Med. 1996 Jul 4;335(1):54-5. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Department of Medicine, University Hospital, Groningen, The Netherlands.BACKGROUND: Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis

in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial. METHODS: We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially. RESULTS: Forty-one patients were assigned to receive co-trimoxazole,

and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse. CONCLUSIONS:

Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.PMID: 8637536 [PubMed - indexed for MEDLINE]========================Arch Otolaryngol Head Neck Surg. 1993 Jan;119(1):103-5. Links Long-term sulfamethoxazole-trimethoprim in Wegener's granulomatosis.McRae D, Buchanan G. Ear, Nose, and Throat Department, Southend Hospital, Westcliff-on-Sea, England.Since 1985, a number of reports have highlighted the effectiveness of a short course of sulfamethoxazole-trimethoprim as an adjuvant to immunosuppressive drugs in the treatment of Wegener's granulomatosis. We report our experience with long-term sulfamethoxazole-trimethoprim therapy in patients with Wegener's granulomatosis. We describe recent advances in the pathogenesis of Wegener's granulomatosis, suggest a complementary mechanism of action of

sulfamethoxazole-trimethoprim, and advocate long-term sulfamethoxazole-trimethoprim therapy as a treatment option in Wegener's granulomatosis.PMID: 8417733 [PubMed - indexed for MEDLINE]