Reports of clinical relapse occurring after apparently successful
antibiotic treatment of
Whipple's disease prompted this review of long-term follow-up of treated patients. Follow-up of at least 1 yr after completion of treatment or 2 yr after diagnosis was obtained on 88 patients with documented
Whipple's disease by a review of the medical literature, correspondence with the authors as needed, and questionnaires mailed to academic gastroenterology programs in the United States. Relapse was defined on the basis of morphology (preferably) or clinically, or both. Thirty-one patients relapsed, 6 of whom relapsed twice. Fifty-seven patients did not relapse. The mean time to relapse was 4.2 yr. The mean follow-up period of patients who did not relapse was 8.2 yr. The type and number of relapses were as follows: clinical, 16; central nervous system, 13;
arthralgia, 5; gastrointestinal, 1; and cardiac, 2. The clinical,
arthralgia, and gastrointestinal relapses were evenly distributed between early relapses (occurring less than 2 yr after diagnosis) and late relapses (occurring greater than 2 yr after diagnosis). All cardiac and central nervous system relapses were late. Twenty-one of 49 patients treated with
tetracycline alone relapsed. Two relapses were reported in 15 patients treated with
penicillin and
streptomycin followed by
tetracycline. Three relapses developed in 8 patients treated with
penicillin alone. Five of the 16 patients treated with other regimens relapsed. Nine of the 13 patients with central nervous system relapse had been initially treated with
tetracycline, 2 were treated with
penicillin, and 2 were treated with combinations of
antibiotics. Results of treatment of central nervous system relapse were poor in 10 of the 11 patients for whom details were available. Results of treatment of non-central-nervous-system relapse were excellent in 19 of 20 patients. It is concluded that
tetracycline alone, or
penicillin alone, is not adequate initial
therapy for
Whipple's disease and that central nervous system relapse is resistant to
antibiotic therapy. The authors recommend parenteral
penicillin and
streptomycin followed by 1 yr of oral
trimethoprim-sulfamethoxazole therapy or oral
trimethoprim-sulfamethoxazole alone for 1 yr as initial
therapy for
Whipple's disease. Relapse should be defined by demonstration of recurrence of bacilli whenever possible.