Digestive Diseases and Sciences

, Volume 39, Issue 8, pp 1642–1648 | Cite as

An evaluation of antimicrobial treatment for whipple's disease

Tetracycline versus trimethoprim-sulfamethoxazole
  • Gerhard E. Feurle
  • Thomas Marth
Original Articles


Whipple's disease is a multisystemic disorder in which almost all organ systems can be invaded by rod-shaped bacteria. Without extended antimicrobial therapy, its course is lethal. Empirically, treatment consists of tetracyclines given for one to two years. Trimethoprim-sulfamethoxazole, a compound that crosses the blood-brain barrier, has been suggested as an alternative when patients were observed with progressive cerebral involvement. There has never been a formal evaluation of the selection of antibiotics for the treatment of Whipple's disease. In the present nonrandomized, partially retrospective study, we compared the result of two treatment regimens in 30 patients, all examined personally. Twenty-two patients were treated with tetracycline and eight patients with trimethoprim-sulfamethoxazole. In five patients, therapy with tetracycline was changed to another antimicrobial agent because of treatment failure or drug intolerance. The main treatment measure was disappearance of the clinical symptoms such as weight loss, arthritis, malabsorption, fever, edema, central nervous system manifestations, lymphadenopathy, and congestive heart failure. Drug intolerance requiring a change of medication was also considered a treatment failure. We found that trimethoprim-sulfamethoxazole induced complete clinical remission in 12 of 13 treatment cycles, tetracycline in 13 of 22 treatment cycles (P<0.05; mean difference 33%; 95% confidence interval 8% to 58%). Trimethoprim-sulfamethoxazole was also more efficacious than tetracycline in the treatment of cerebral Whipple's disease. However, trimethoprim-sulfamethoxazole did not prevent cerebral manifestations in all cases. The only deaths due to Whipple's disease occurred in patients with cerebral involvement. It is concluded that treatment with trimethoprim-sulfamethoxazole was significantly superior to that with tetracycline in inducing clinical remission of Whipple's disease. A more active antimicrobial regimen is necessary to treat cerebral involvement.

Key words

Whipple's disease treatment tetracycline trimethoprim-sulfamethoxazole co-trimoxazole therapy 


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  1. 1.
    Relman DA, Schmidt TM, MacDermott RP, Falkow S: Identification of the uncultured bacillus of Whipple's disease. N Engl J Med 327:293–301, 1992Google Scholar
  2. 2.
    Paulley JW: A case of Whipple's disease (intestinal lipodystrophy). Gastroenterology 22:128–133, 1952Google Scholar
  3. 3.
    Ruffin JM, Kurtz SM, Roufail WM: Intestinal lipodystrophy (Whipple's disease)—the immediate and prolonged effect of antibiotic therapy. JAMA 195:182–184, 1966Google Scholar
  4. 4.
    Maizel H, Ruffin JM, Dobbins WO III: Whipple's disease: A review of 19 patients from one hospital and a review of the literature since 1950. Medicine 42:175–205, 1970Google Scholar
  5. 5.
    Schur P: Psoriatic arthritis and arthritis associated with gastrointestinal diseasesIn Harrison's Principles of Internal Medicine, 12th ed. JD Wilson, E Braunwald, KJ Isselbacher, RG Petersdorf, JB Martin, AS Fauci, RK Root (ed). McGraw-Hill, New York, 1991. pp 1482–1484Google Scholar
  6. 6.
    Bai JC, Crosetti EE, Maurino EC, Martinez CA, Sambuelli SA, Boerr LA: Short-term antibiotic treatment in Whipple's disease. J Clin Gastroenterol 13:303–307, 1991Google Scholar
  7. 7.
    Fleming JL, Wiesner RH, Shorter RG: Whipple's disease: Clinical, biochemical and histopathologic features and assessment of treatment in 29 patients. Mayo Clin Proc 63:539–551, 1988Google Scholar
  8. 8.
    Keinath RD, Merrell DE, Vliestra R, Dobbins WO III: Antibiotic treatment and relapse in Whipple's disease. Gastroenterology 88:1867–1873, 1985Google Scholar
  9. 9.
    Knox DL, Bayless TM, Yardley JH, Charache P: Whipple's disease presenting with ocular inflammation and minimal intestinal symptoms. John Hopkins Med J 123:175–181, 1968Google Scholar
  10. 10.
    Knox DL, Bayless TM, Pittman FE: Neurologic disease in patients with treated Whipple's disease. Medicine 55:467–476, 1976Google Scholar
  11. 11.
    Feurle GE, Volk B, Waldherr R: Cerebral Whipple's disease with negative jejunal histology. N Engl J Med 300:907–908, 1979Google Scholar
  12. 12.
    Barling RWA, Selkon JB: The penetration of antibiotics into cerebrospinal fluid and brain tissue. J Antimicrobiol Chemother 4:203–227, 1978Google Scholar
  13. 13.
    Wang EEL, Prober CG: Ventricular cerebrospinal fluid concentrations of trimethoprim-sulfamethoxazole. J Antimicrobiol Chemother 11:385–389, 1983Google Scholar
  14. 14.
    Feurle GE: Morbus Whipple. Handbuch der Inneren Medizin Bd. III/3. B. Dünndarm. Berlin, Springer-Verlag, 1983, pp 85–104Google Scholar
  15. 15.
    Elsborg L, Gravgaard E, Jacobson NO: Treatment of Whipple's disease with sulfamethoxazole-trimethoprim. Acta Med Scand 198:141–143, 1975Google Scholar
  16. 16.
    Tauris P, Moesner J: Whipple's disease—clinical and histopathological changes during treatment with sulfamethoxazole-trimethoprim. Acta Med Scand 204:423–427, 1978Google Scholar
  17. 17.
    Viteri AL, Greene JF, Chandler JB: Whipple's disease, successful response to sulfamethoxazole-trimethoprim. Am J Gastroenterol 75:309–310, 1981Google Scholar
  18. 18.
    Ryser RJ, Locksley RM, Eng SC, Dobbins WO III, Schoenknecht FD, Rubin CE: Reversal of dementia associated with Whipple's disease by trimethoprim-sulfamethoxazole, drugs that penetrate the blood-brain barrier. Gastroenterology 86:745–752, 1984Google Scholar
  19. 19.
    Krücke W, Stochdorph O: Über Veränderungen im Zentralnervensystem bei Whipple'scher Krankheit. Verh Dtsch Ges Pathol 46:198–202, 1962Google Scholar
  20. 20.
    Lapointe LR, Lamarche J, Salloum A, Beaudry R: Meningoependymitis in Whipple's disease. J Can Sci Neurol 7:163–167, 1980Google Scholar
  21. 21.
    Romanul FCA, Radvany J, Rosales RK: Whipple's disease confined to the brain: A case studied clinically and pathologically. J Neurol Neurosurg 40:901–909, 1977Google Scholar
  22. 22.
    Powers JM, Rawe SE: A neuropathologic study of Whipple's disease. Acta Neuropathol 48:223–226, 1979Google Scholar
  23. 23.
    Simberkoff MS, Moldover NH, Rahal JJ Jr: Absence of detectable bactericidal and opsonic activities in normal and infected human cerebrospinal fluids: A regional host defense deficiency. J Lab Clin Med 95:362–372, 1980Google Scholar
  24. 24.
    Martin FF, Vilseck J, Dobbins WO III, Buckley CE, Tyor MP: Immunological alteration in patients with treated Whipple's disease. Gastroenterology 63:6–18, 1972Google Scholar
  25. 25.
    Feurle GE, Dörken B, Schöpf E, Lenhard V: HLA B27 and defects in the T-cell system in Whipple's disease. Eur J Clin Invest 9:385–389, 1979Google Scholar
  26. 26.
    Marth T, Feurle GE, Roux M, Meuer SC: Impaired interaction of immunocompetent cells in Whipple's disease. Immunobiology 183:239–240, 1991 (abstract)Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Gerhard E. Feurle
    • 1
  • Thomas Marth
    • 1
  1. 1.From the Stadtkrankenhaus NeuwiedUniversity of BonnBonnGermany

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