Current Allergy and Asthma Reports

, Volume 1, Issue 6, pp 566–571 | Cite as

The diagnosis and treatment of whipple’s disease

  • Thomas Marth
Article

Abstract

Whipple’s disease is a rare, chronic, and systemic infectious disease caused by the ubiquitously occuring bacterium Tropheryma whippelii. For two reasons, the disease represents a good example for documenting the input of modern molecular-based techniques into pathogenetic, diagnostic, and therapeutic concepts in clinical medicine. First, the unidentified and uncultivable causative organism has been characterized by novel molecular-genetic techniques. Second, in contrast to other chronic inflammatory disorders, clinical manifestations of T. whippelii infection seem to be based on reduced T-cell helper type 1 (TH1) activity. These findings have led to an improved pathophysiologic understanding of the disease and to new aspects in treatment strategies that are discussed in this paper.

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References and Recommended Reading

  1. 1.
    Dobbins WO III: Whipple’s DiseaseIn. Springfield, IL: Charles C Thomas; 1987.Google Scholar
  2. 2.
    Marth T: Whipple’s disease. In Principles and Practice of Infectious Disease, edn. 5. Edited by Mandell GL, Dolin R, Bennett JE.Philadelphia: Churchill Livingstone; 1999: 1170–1174.Google Scholar
  3. 3.
    Feurle GE, Marth T: An evaluation of antimicrobial treatment for Whipple’s disease—tetracycline versus trimethoprim-sulfamethoxazole. Dig Dis Sci 1994, 39:1642–1648.A large retrospective therapy study emphasizing the superior role of trimethoprim-sulfamethoxazole over tetracycline in the primary treatment of Whipple’s disease and the treatment of relapse.PubMedCrossRefGoogle Scholar
  4. 4.
    Fleming JL, Wiesner RH, Shorter RG: Whipple’s disease: clinical, biochemical and histopathological features and assessment of treatment in 29 patients. Mayo Clin Proc 1988, 63:539–551.PubMedGoogle Scholar
  5. 5.
    Martin FF, Vilseck J, Dobbins WO III, et al.: Immunological alterations in patients with treated Whipple’s disease. Gastroenterology 1972, 63:6–18.PubMedGoogle Scholar
  6. 6.
    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 1979, 9:385–389.PubMedCrossRefGoogle Scholar
  7. 7.
    Marth T, Roux M, von Herbay A, et al.: Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple’s disease. Clin Immunol Immunopathol 1994, 72:217–226.PubMedCrossRefGoogle Scholar
  8. 8.
    Maiwald M, Meier-Willersen HJ, Hartmann M, von Herbay A: Detection of Tropheryma whippelii DNA in a patient with AIDS. J Clin Microbiol 1995, 33:1354–1356.PubMedGoogle Scholar
  9. 9.
    Rosenblatt HM: Immunodeficiencies associated with medical therapy. In Handbook of Mucosal Immunology. Edited by Ogra PL,McGhee JR, Mestecky J, et al. San Diego: Academic Press;1994:824–835.Google Scholar
  10. 10.
    Gross JB, Wollaeger EE, Sauer WG, et al.: Whipple’s disease: report of four cases, including two brothers, with observations on patholgic physiology, diagnosis, and treatment. Gastroenterology 1959, 36:65–93.PubMedGoogle Scholar
  11. 11.
    Meier-Willersen HJ, Maiwald M, von Herbay A: Whipple’s disease associated with opportunistic infections [in German]. Dtsch Med Wochenschr 1993, 113:854–860.CrossRefGoogle Scholar
  12. 12.
    Geboes K, Ectors N, Heidbuchel H, et al.: Whipple’s disease: the value of upper gastrointestinal endoscopy for the diagnosis and follow-up. Acta Gastroenterol Belg 1992, 55:209–219.PubMedGoogle Scholar
  13. 13.
    Relman DA, Schmidt TM, Macdermott RP, Falkow S: Identification of the uncultured bacillus of Whipple’s disease. New Engl J Med 1992, 327:293–301.phylogenetic classification of the up to the year 2000 uncultivable causative bacterium as an actinomycetes based on analysis of the bacterial 16rRNA with the use of broad range and specific primers. Based on this work, specific detection of T. whippelii in specimens by PCR became available.PubMedCrossRefGoogle Scholar
  14. 14.
    Ramzan NN, Loftus E, Burgart LJ, et al.: Diagnosis and monitoring of Whipple’s disease by polymerase chain reaction. Ann Intern Med 1997, 126:520–527.Describes the use of PCR in a larger group to diagnose and monitor Whipple’s disease in gastrointetstinal and cerebrospinal fluid specimens and compares it with conventional histopathological diagnosis.PubMedGoogle Scholar
  15. 15.
    von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M: Whipple’s disease: staging and monitoring by cytology and polymerase chain reaction of cerebrospinal fluid. Gastroenterology 1997, 113:434–441.CrossRefGoogle Scholar
  16. 16.
    Lowsky R, Archer GL, Fyles G, et al.: Diagnosis of Whipple’s disease by molecular analysis of peripheral blood. N Engl J Med 1994, 331:1343–1346.PubMedCrossRefGoogle Scholar
  17. 17.
    Marth T, Fredericks D, Strober W, Relman DA: Limited role for PCR-based diagnosis of Whipple’s disease from peripheral blood mononuclear cells. Lancet 1996, 348:66–67.PubMedCrossRefGoogle Scholar
  18. 18.
    Raoult D, Lepidi H, Harle JR: Tropheryma whippelii circulating in blood monocytes. New Engl J Med 2001, 345:548.PubMedCrossRefGoogle Scholar
  19. 19.
    Silva MT, Macedo PM, Nunes JFM: Ultrastructure of bacilli and bacillary origin of the macrophagic inclusions in Whipple’s disease. J Gen Microbiol 1985, 131:1001–1013.PubMedGoogle Scholar
  20. 20.
    Dobbins WO III, Ruffin JM: A light- and electron-microscopic study of bacterial invasion in Whipple’s disease. Am J Pathol 1967, 51:225–242.PubMedGoogle Scholar
  21. 21.
    Trier JS, Phelps PC, Eidelmann S, Rubin CE: Whipple’s disease: light and electron microscope correlation of jejunal mucosal histology with antibiotic treatment and clinical status. Gastroenterology 1965, 48:684–707.PubMedGoogle Scholar
  22. 22.
    Wilson KH, Blitchington R, Frothingham R, Wilson JAP: Phylogeny of the Whipple’s disease-associated bacterium. Lancet 1991, 338:474–475.PubMedCrossRefGoogle Scholar
  23. 23.
    Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A: Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1998, 64:760–762.PubMedGoogle Scholar
  24. 24.
    Dutly F, Hinrikson HP, Seidel T, et al.: Tropheryma whippelii DNA in saliva of patients without Whipple’s disease. Infection 2000, 28:219–222.PubMedCrossRefGoogle Scholar
  25. 25.
    Hinrikson HP, Dutly F, Altwegg M: Evaluation of a specific nested PCR targeting domain III of the 23S rRNA gene of "Tropheryma whippelii" and proposal of a classification system for its molecular variants. J Clin Microbiol 2000, 38:595–599.PubMedGoogle Scholar
  26. 26.
    Schoedon G, Goldenberger D, Forrer R, et al.: Deactivation of macrophages with interleukin-4 is the key to the isolation of pheryma whippelii J Infect Dis 1997, 176:672–677.ports depressed TH1 cytokines and increased TH2 responses as requirements to grow the bacterium in vitro.PubMedGoogle Scholar
  27. 27.
    Raoult D, Birg ML, La Scola B, et al.: Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000, 342:620–625.The first successful growth and propagation of T. whippelii in vitro with the use of special centrifuge and cell culture techniques. In this paper, the first polyclonal antibodies also have been generated; ie, IgM antibodies show specific reactivity to sera/tissue of Whipple’s disease patients, and IgG antibodies react to sera of many healthy subjects.PubMedCrossRefGoogle Scholar
  28. 28.
    Ectors N, Geboes K, De Vos R, et al.: Whipple’s disease: a histological, immunocytochemical and electron microscopic study of the immune response in the small intestinal mucosa. Histopathology 1992, 21:1–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Marth T, Neurath M, Cuccherini BA, Strober W: Defects of monocyte interleukin-12 production and humoral immunity in Whipple’s disease. Gastroenterology 1997, 113:442–448.Shows that an impaired function of antigen-presenting cells in Whipple’s disease may be related to a reduced macrophage IL-12 production with secondary impaired cell-mediated immune responses including IFN-g secretion and decreased IgG2 subclass levels.PubMedCrossRefGoogle Scholar
  30. 30.
    Schneider T, Stallmach A, von Herbay A, et al.: Treatment of refractory Whipple’s disease with recombinant interferongamma. Ann Intern Med 1998, 129:875–877.PubMedGoogle Scholar
  31. 31.
    Keinath RD, Merrell DE, Vlietstra R, Dobbins WO III: Antibiotic treatment and relapse in Whipple’s disease. Gastroenterology 1985, 88:1867–1873.PubMedGoogle Scholar
  32. 32.
    Misbah SA, Mapstone NP: Whipple’s disease revisited. J Clin Pathol 2000; 53:750–755.PubMedCrossRefGoogle Scholar
  33. 33.
    Feurle GE, Volk B, Waldherr R: Cerebral Whipple’s disease with negative jejunal histology. N Engl J Med 1979, 300:907–908.Points to the protean nature of the disorder in that the dangerous and in many cases progressive CNS manifestations may occur in the absence of "typical" clinical Whipple’s disease features.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2001

Authors and Affiliations

  • Thomas Marth
    • 1
  1. 1.Deutsche Klinik für DiagnostikWiesbadenGermany

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