Current Infectious Disease Reports

, Volume 8, Issue 2, pp 96–102

Whipple’s disease

  • Klaus Mönkemüller
  • Lucía C. Fry
  • Steffen Rickes
  • Peter Malfertheiner
Article

Abstract

Whipple’s disease (WD) is a chronic debilitating disease caused by the bacillus Tropheryma whippleii. WD classically presents with the main clinical symptoms of polyarthralgias, chronic diarrhea, weight loss, and abdominal pain. Given its systemic involvement, it is common for WD to present with a multitude of other clinical scenarios—sometimes with predominant neurologic, cardiac, and dermatologic manifestations. WD can occur at any age, but it generally occurs during the fifth decade and predominantly in men. The diagnosis of WD is established by demonstrating the organism on biopsies from the involved system, by histology, electron microscopy, polymerase chain reaction, and more recently, by culture of bacteria. The histologic features include a coarse granular cytoplasm and foamy macrophages that stain strongly with the period-acid Schiff reagent. Current therapy includes an initial 2-week course of intravenous cephalosporins followed by 1-year oral trimethoprim-sulfamethoxazole.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Dobbins WO: Whipple’s disease: an historical perspective. Q J Med 1985, 56:523–531.PubMedGoogle Scholar
  2. 2.
    Mahnel R, Marth T: Progress, problems, and perspectives in diagnosis and treatment of Whipple’s disease. Clin Exp Med 2004, 4:39–43.PubMedCrossRefGoogle Scholar
  3. 3.
    Durand DV, Lecomte C, Cathebras P, et al.: Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Medicine 1997, 76:170–184.PubMedCrossRefGoogle Scholar
  4. 4.
    Fenollar F, Raoult D: Whipple’s disease. Curr Gastroenterol Rep 2003, 5:379–385.PubMedCrossRefGoogle Scholar
  5. 5.
    Misbah SA, Ozols B, Franks A, Mapstone N: Whipple’s disease without malabsorption: new atypical features. QJ Med 1997, 90:765–772.Google Scholar
  6. 6.
    Schneider T, Salomon-Looijen M, von Herbay A, et al.: Whipple’s disease with aortic regurgitation requiring aortic valve replacement. Infection 1998, 26:178–180.PubMedGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    La Scola B, Fenollar F, Fournier PE, et al.: Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple’s disease bacillus. Int J Syst Evol Microbiol 2001, 51:1471–1479.PubMedGoogle Scholar
  9. 9.
    Relman DA, Schmidt TM, MacDermott RO, Falkow S: Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992, 327:293–301. This is one of the classic articles describing the Identification of Whipple’s bacillus. It will be always considered a landmark paper.PubMedCrossRefGoogle Scholar
  10. 10.
    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
  11. 11.
    von Herbay A, Ditton HJ, Maiwald M: Diagnostic application of a polymerase chain reaction assay for the Whipple’s disease bacterium to intestinal biopsies. Gastroenterology 1996, 110:1735–1743.CrossRefGoogle Scholar
  12. 12.
    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
  13. 13.
    Feurle GE, Marth T: An evaluation of antimicrobial treatment for Whipple’s disease: tetracycline versus trimethoprim-sulfamethoxazole. Dig Dis Sci 1994, 39:1642–1648.PubMedCrossRefGoogle Scholar
  14. 14.
    Elsborg L, Gravgaard E, Jacobsen NO: Treatment of Whipple’s disease with sulfamethoxazole-trimethoprim. Acta Med Scand 1975, 198:141–143.PubMedCrossRefGoogle Scholar
  15. 15.
    Schnider PJ, Reisinger EC, Gerschlager W, et al.: Long-term follow up in cerebral Whipple’s disease. Eur J Gastroenterol Hepatol 1996, 8:899–903.PubMedGoogle Scholar
  16. 16.
    Brühlmann P, Michel BA, Altwegg M: Diagnosis and therapy monitoring of Whipple’s arthritis by polymerase chain reaction. Rheumatology 2000, 39:1427–1428. This article discusses the uses and limitations of PCR for the diagnosis and therapy of Whipple’s disease.PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    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.PubMedGoogle Scholar
  19. 19.
    Keinath RD, Merrell DE, Vlietstra R, Dobbins III WO: Antibiotic treatment and relapse in Whipple’s disease. Gastroenterology 1985, 88:1867–1873.PubMedGoogle Scholar
  20. 20.
    Marth T, Raoult D: Whipple’s disease. Lancet 2003, 361:239–246. One of the best review articles written by world renowned experts in Whipple’s disease. The sections of microbiology, immunology, and PCR are particularly interesting and useful for the basic scientist as well as the clinician.PubMedCrossRefGoogle Scholar
  21. 21.
    Dutly F, Altwegg M: Whipple’s disease and “Tropheryma whippelii.” Clin Microbiol Rev 2001, 14:561–583. This excellent, extensive review covers all aspects of Whipple’s disease.PubMedCrossRefGoogle Scholar
  22. 22.
    Bai JC, Mazure RM, Vazquez H, et al.: Whipple’s disease. Curr Gastroenterol Hepatol 2004, 2:849–860. Very well written review of Whipple’s disease.CrossRefGoogle Scholar
  23. 23.
    Paulley JW: A case of Whipple’s disease (intestinal lipodystrophy). Gastroenterology 1952, 22:128–133.PubMedGoogle Scholar
  24. 24.
    Misbah SA, Mapstone NP: Whipple’s disease revisited. J Clin Pathol 2000, 53:750–755. Very practical review of Whipple’s disease. Most useful for the clinician.PubMedCrossRefGoogle Scholar
  25. 25.
    Wilson KH, Blitchington R, Frothingham R, et al.: Phylogeny of the Whipple’s-disease-associated bacterium. Lancet 1991, 328:474–475.CrossRefGoogle Scholar
  26. 26.
    Schoedon G, Goldenberger D, Forrer R, et al.: Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii. J Infect Dis 1997, 176:672–677.PubMedGoogle Scholar
  27. 27.
    Bentley SD, Maiwald M, Murphy LD, et al.: Sequencing and analysis of the genome of the Whipple’s disease bacterium Tropheryma whipplei. Lancet 2003, 361:637–644. Landmark paper describing the decoding of the genetic sequence of T. whippleii.PubMedCrossRefGoogle Scholar
  28. 28.
    von Herbay A, Otto HF, Stolte M, et al.: Epidemiology of Whipple’s disease in Germany: analysis of 110 patients diagnosed in 1965–1995. Scand J Gastroenterol 1997, 32:52–57. One of the most thorough epidemiologic investigations of Whipple’s disease, it encompasses one of the largest worldwide experiences of this disease.Google Scholar
  29. 29.
    Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A: Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1999, 64:760–762.Google Scholar
  30. 30.
    Gross JB, Wollaeger EE, Sauer WG, et al.: Whipple’s disease: report of four cases, including two brothers, with observations on pathologic physiology, diagnosis and treatment. Gastroenterology 1959, 36:65–93.PubMedGoogle Scholar
  31. 31.
    Dykmann DD, Cuccherini BA, Fuss IJ, et al.: Whipple’s disease in a father-daughter pair. Dig Dis Sci 1999, 44:2542–2544.CrossRefGoogle Scholar
  32. 32.
    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
  33. 33.
    Bai JC, Mota AH, Maurino E, et al.: Class I and class II HLA antigens in a homogenous Argentinean population with Whipple’s disease: lack of association with HLAB27. Am J Gastroenterol 1991, 86:992–994.PubMedGoogle Scholar
  34. 34.
    Street S, Donoghue HD, Neild GH: Tropheryma whippelii DNA in saliva of healthy people. Lancet 1999, 354:1178–1179.PubMedCrossRefGoogle Scholar
  35. 35.
    Maiwald M, Ditton HJ, von Herbay A, et al.: Reassessment of the phylogenetic position of the bacterium associated with Whipple’s disease and determination of the 16S-23S ribosomal intergenic spacer sequence. Int J Syst Bacteriol 1996, 46:1078–1082.PubMedCrossRefGoogle Scholar
  36. 36.
    Khavari PA, Bolognia JL, Eisen R, et al.: Periodic acid-Schiff positive organisms in primary cutaneous Bacillus cereus infection-case report and an investigation of periodic acid-Schiff staining properties of bacteria. Arch Dermatol 1991, 127:543–546.PubMedCrossRefGoogle Scholar
  37. 37.
    Kent SP, Kirkpatrick PM: Whipple’s disease: immunological and histochemical studies of eight cases. Arch Pathol Lab Med 1980, 104:544–547.PubMedGoogle Scholar
  38. 38.
    Ghigo E, Capo C, Aurouze M, et al.: The survival of Tropheryma whipplei, the agent of Whipple’s disease, requires phagosome acidification. Infect Immun 2002, 70:1501–1506.PubMedCrossRefGoogle Scholar
  39. 39.
    Eck M, Kreipe H, Harmsen D, Müller-Hermelink HK: Invasion and destruction of mucosal plasma cells by Tropheryma whippelii. Hum Pathol 1997, 28:1424–1428.PubMedCrossRefGoogle Scholar
  40. 40.
    Marth T, Kleen N, Stallmach A, et al.: Dysregulated peripheral and mucosal Th1/Th2 response in Whipple’s disease. Gastroenterology 2002, 123:1468–1477.PubMedCrossRefGoogle Scholar
  41. 41.
    Mahnel R, Kalt A, Ring S, et al.: Immunosuppressive therapy in Whipple’s disease patients is associated with the appearance of gastrointestinal manifestations. Am J Gastroenterol 2005, 100:1167–1173.PubMedCrossRefGoogle Scholar
  42. 42.
    Louis ED, Lynch T, Kaufmann P, et al.: Diagnostic guidelines in central nervous system Whipple’s disease. Ann Neurol 1996, 40:561–568.PubMedCrossRefGoogle Scholar
  43. 43.
    Chears WC, Ashworth CT: Electron microscopy study of the intestinal mucosa in Whipple’s disease: demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology 1961, 41:129–138.PubMedGoogle Scholar
  44. 44.
    Fry LC, Curioso WH, Lazenby AJ, Mönkemüller KE: Whipple’s disease. Gastrointest Endosc 2004, 59:538–539.PubMedCrossRefGoogle Scholar
  45. 45.
    LeVine ME, Dobbins WO: Joint changes in Whipple’s disease. Semin Arthritis Rheum 1973, 3:79–93.PubMedCrossRefGoogle Scholar
  46. 46.
    Pron B, Poyart C, Abachin E, et al.: Diagnosis and followup of Whipple’s disease by ampli.cation of the 16S rRNA gene of Tropheryma whippelii. Eur J Clin Microbiol Infect Dis 1999, 18:62–65.PubMedCrossRefGoogle Scholar
  47. 47.
    Schwartz MA, Selhorst JB, Ochs AL, et al.: Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple’s disease. Ann Neurol 1986, 20:677–683.PubMedCrossRefGoogle Scholar
  48. 48.
    Suzer T, Demirkan N, Tahta K, et al.: Whipple’s disease con.ned to the central nervous system: case report and review of the literature. Scan J Infect Dis 1999, 31:411–414.CrossRefGoogle Scholar
  49. 49.
    Müller N, Schneider T, Zeitz M, Marth T: Whipple’s disease: new aspects in pathogenesis and diagnosis. Acta Endoscopica 2001, 31:243–253.CrossRefGoogle Scholar
  50. 50.
    Schneider T, Stallmach A, von Herbay A, et al.: Treatment of refractory Whipple disease with interferon-gamma. Ann Intern Med 1998, 129:875–877.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Klaus Mönkemüller
    • 1
  • Lucía C. Fry
  • Steffen Rickes
  • Peter Malfertheiner
  1. 1.Department of Gastroenterology, Hepatology and Infectious DiseasesOtto-von-Guericke-University of MagdeburgMagdeburgGermany

Personalised recommendations