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

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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 Reports

PMID: 3871238 [PubMed - indexed for MEDLINE]

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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]

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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 F

PMID: 3044373 [PubMed - indexed for MEDLINE]

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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]

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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]

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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]

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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]

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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]