Clinical Reviews
Medwave 2011;11(08):e5112 doi: 10.5867/medwave.2011.08.5112
Definitions and Perspectives of Whipple's Disease
Marco Esteban Gudiño Gomezjurado (1) Alvaro Francisco Gudiño Gomezjurado (2)
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Key Words: Whipple’s disease, physiopathology, therapeutics

Abstract

Whipple’s disease can involve any organ of the human economy thanks to the ability of the bacteria that causes it to evade the host immune system. Since its discovery to present the diagnosis and treatment have become a real challenge, though important, what it represents in the patient's prognosis. The aim of this paper is to review the pathogenesis, diagnostic and therapeutic options in the light of current evidence.


 

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La enfermedad de Whipple es capaz de comprometer cualquier órgano de la economía humana gracias a la capacidad que tiene la bacteria que la ocasiona para esquivar el sistema inmune del hospedador. Desde su descubrimiento hasta la actualidad el diagnóstico y el tratamiento se han constituido en un auténtico reto, siendo importante lo que esto representa en el pronóstico del paciente. El objetivo de este artículo es revisar la patogenia, las alternativas diagnósticas y las opciones terapéuticas a la luz de la evidencia actual.

Authors: Marco Esteban Gudiño Gomezjurado (1) Alvaro Francisco Gudiño Gomezjurado (2)

Affiliation:
[1] Universidad Federal de Lavras, Lavras, Brasil.
[2] Posgrado de Medicina Interna, Pontificia Universidad Católica del Ecuador, Puce, Ecuador; Hospital General Enrique Garcés, Quito, Ecuador.

E-mail: 584alvaro@gmail.com

Citation: Gudiño, M. Gudiño, A. Fisiopatología, diagnóstico y tratamiento de la enfermedad de whipple. Medwave 2011;11(08). Gudiño , Gudiño . Pathophysiology, diagnosis and treatment of Whipple's disease. Medwave 2011;11(08):e5112 doi: 10.5867/medwave.2011.08.5112

Submission date: 10/6/2011

Acceptance date: 21/7/2011

Publication date: 31/7/2011

Origin: not commissioned, submitted through FTS

Type of review: externally peer-reviewed, 3 reviewers, double-blind


 

Errata

1. Se corrigen los nombres de los autores y sus respectivas filiaciones. | Link |

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  1. Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar;8(3):179-90. | CrossRef | PubMed |
  2. Knaapen HK, Barrera P. Therapy for Whipple's disease. J Antimicrob Chemother. 2007 Sep;60(3):457-8. Epub 2007 Jul 10. | CrossRef | PubMed |
  3. Boulos A, Rolain JM, Raoult D. Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. Antimicrob Agents Chemother. 2004 Mar;48(3):747-52. | CrossRef | PubMed | PMC |
  4. Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic Tropheryma whipplei Clinical Presentation of 142 Patients with infections diagnosed or confirmed in a reference center. Medicine 2010; (89): 337-345. | CrossRef | PubMed |
  5. Desnues B, Al Moussawi K, Fenollar F. New insights into Whipple’s disease and Tropheryma whipplei infections. Microbes and Infection 2010; (12) 1102-1110. | CrossRef | PubMed |
  6. Lagier JC, Fenollar F, Lepidi H, Raoult D. Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease. J Antimicrob Chemother. 2010 Sep;65(9):2005-12. | CrossRef | PubMed |
  7. Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. Gastroenterology. 2010 Feb;138(2):478-86; quiz 11-2. Epub 2009 Oct 29. | CrossRef | PubMed |
  8. Bonhomme CJ, Renesto P, Desnues B, Ghigo E, Lepidi H, Fourquet P, Fenollar F, Henrissat B, Mege JL, Raoult D. Tropheryma whipplei glycosylation in the pathophysiologic profile of Whipple's disease. J Infect Dis. 2009 Apr 1;199(7):1043-52. | CrossRef | PubMed |
  9. Gorvel L, Al Moussawi K, Ghigo E, Capo C, Mege JL, Desnues B. Tropheryma whipplei, the Whipple’s disease bacillus, induces macrophage apoptosis through the extrinsic pathway. Cell Death Dis. 2010 Apr 8;1:e34. | CrossRef | PubMed | PMC |
  10. Koligi K, Mertz D, Benz D, Vogt T, Bloemberg GV, Winter L, Tyndall A, Battegay M, Walker UA. Of bugs and joints : Oligoarthritis caused by Tropheryma whipplei. Internist (Berl). 2011 Jul;52(7):884-888. | CrossRef | PubMed |
  11. Jackuliak P, Koller T, Baqi L, Plank L, Lasabova Z, Minarik G, Payer J. Whipple’s Disease Generalized Stage. Dig Dis Sci 2008; (53):3250–3258. | CrossRef | PubMed |
  12. Fenollar F Mediannikov O, Socolovschi C, Bassene H, Diatta G, Herve R et al. Tropheryma whipplei bacteremia during fever in rural West Africa. Clinical Infectious Diseases 2010; (5):515–521. | CrossRef | PubMed |
  13. Rolain JM, Fenollar F, Raoult D. False positive PCR detection of Tropheryma whipplei in the saliva of healthy people, BMC Microbiology 2007; (7):48. | CrossRef | PubMed | PMC |
  14. Fenollar F, Laouira S, Lepidi H, Rolain JM, Raoult D. Value of Tropheryma whipplei Quantitative Polymerase Chain Reaction Assay for the Diagnosis of Whipple Disease: sefulness of Saliva and Stool Specimens for First-Line Screening Clinical Infectious Diseases 2008; (47):659–67. | CrossRef | PubMed |
  15. Tran H. Reversible hypothyroidism and Whipple's disease, BMC Endocrine Disorders 2006; (6):3. | CrossRef | PubMed | PMC |
  16. Hansen A, Mereles D. Cardiac complications in Whipple’s disease, European Journal of Echocardiography 2008; (9): 426–427. | CrossRef | PubMed |
  17. Misbah SA, Ozols B, Franks A, Mapstone N. Whipple's disease without malabsorption: new atypical features. QJM. 1997 Dec;90(12):765-72. | PubMed |
  18. Ratnaike R. Whipples disease. Postgrad Med J 2000;(76):760-766. | CrossRef | PubMed | PMC |
  19. Maiwald M, Relman D. Whipple’s Disease and Tropheryma whippelii: Secrets Slowly Revealed. Clinical Infectious Diseases 2001; (32):457–63. | PubMed |
  20. Panegyres PK, Edis R, Beaman M, Fallon M. Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis. QJM. 2006 Sep;99(9):609-23. Epub 2006 Aug 11. | CrossRef | PubMed |
  21. Müller C, Petermann D, Stain C, Riemer H, Vogelsang H, Schnider P, Zeiler K, Wrba F. Whipple's disease: comparison of histology with diagnosis based on polymerase chain reaction in four consecutive cases. Gut. 1997 Mar;40(3):425-7. | PubMed | PMC |
  22. Knaapen HK, Barrera P. Therapy for Whipple's disease. J Antimicrob Chemother. 2007 Sep;60(3):457-8. Epub 2007 Jul 10. | CrossRef | PubMed |
  23. Fredricks D, Relman D. Localization of Tropheryma whippelii rRNA in Tissues from Patients with Whipple?s Disease. The Journal of Infectious Diseases 2001;(183):1229?37. | CrossRef | PubMed |
  24. La Scola B, Fenollar F, Fournier P, Altwegg M, Mallet M, Raoult D. Description of Tropheryma whipplei gen. nov sp. nov., the Whipple’s disease bacillus. International Journal of Systematic and Evolutionary Microbiology. 2001; (51): 1471–1479. | PubMed |
  25. Panegyres P. Diagnosis and management of Whipples diasease of the brain. Pract Neurol 2008; (8): 311–317. | CrossRef | PubMed |
  26. Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A. Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii). Appl Environ Microbiol. 1998 Feb;64(2):760-2. | PubMed | PMC |
  27. Elkins C, Shuman T, Pirolo J. Cardiac Whipple’s disease without digestive symptoms. Ann Thorac Surg. 1999; (67):250–251. | CrossRef | PubMed |
  28. Desnues B, Ihrig M, Raoult D, Mege JL. Whipple's disease: a macrophage disease. Clin Vaccine Immunol. 2006 Feb;13(2):170-8. | CrossRef | PubMed | PMC |
  29. Kramer L, Manschot T, Barendregt J , Smit J. Whipple’s disease often a late diagnosis and a rare cause of nephropathy. NDT Plus 2009; (2): 55–58
  30. Fenollar F, Lepidi H, Raoult D, Whipple’s Endocarditis Review of the Literature and Comparisons with Q Fever Bartonella Infection, and Blood Culture–Positive Endocarditis. Clinical Infectious Diseases. 2001; (33): 1309–16. | CrossRef | PubMed |
  31. Di Sabatino A, Vidali F, Cazzola P, Marchese A, Biancheri P, Biagi F, Corazza GR. Splenic hypofunction in Whipple's disease. Am J Gastroenterol. 2009 Oct;104(10):2641-3. | CrossRef | PubMed |
  32. Mahnel R, Kalt A, Ring S, Stallmach A, Strober W, Marth T. Inmunosuppresive therapy in Whipples disease patients in associated with the appearance of gastrointestinal manifestations. Am J Gastroenterol. 2005; (100):1167-1173. | CrossRef | PubMed |
  33. Fenollar F, Raoult D. Infection: How should classic Whipple disease be managed? Nat Rev Gastroenterol Hepatol. 2010 May;7(5):246-8. | CrossRef | PubMed |
  34. Basagiannis C, Panagoulias G, Tentolouris N, Basoukeas S, Sambaziotis D, Spiros L. Whipple Disease. Southern Medical Journal. Apr 2010; (103): 353-356. | CrossRef | PubMed |
  35. Panegyres P, Jonathan F, Fallon M, Connor C. The Amnesic Syndrome of Primary Whipple Disease of the Brain. Cog Behav Neurol. 2010; (23):49–51. | CrossRef | PubMed |
  36. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol. 2009 May 7;15(17):2078-80. | CrossRef | PubMed | PMC |
  37. Baisden B, Lepidi H, Raoult D, Argani P, Yardley JH, Dumler J. Diagnosis of Whipple Disease by Immunohistochemical Analysis. Am J Clin Pathol 2002; (118):742-748. | PubMed |
  38. Desnues B, Raoult D, Mege JL. IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease. J Immunol 2005;(175):4575-4582. | PubMed |
  39. Moos V, Kunkel D, Marth T, Feurle GE, LaScola B, Ignatius R, Zeitz M, Schneider T. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease. J Immunol. 2006 Aug 1;177(3):2015-22. | PubMed |
  40. Feurle GE, Moos V, Schinnerling K, Geelhaar A, Allers K, Biagi F, Bläker H, Moter A, Loddenkemper C, Jansen A, Schneider T. The immune reconstitution inflammatory syndrome in whipple disease: a cohort study. Ann Intern Med. 2010 Dec 7;153(11):710-7. | PubMed |
  41. Dutly F, Altwegg M. Whipple's disease and "Tropheryma whippelii". Clin Microbiol Rev. 2001 Jul;14(3):561-83. | CrossRef | PubMed | PMC |
Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar;8(3):179-90. | CrossRef | PubMed |

Knaapen HK, Barrera P. Therapy for Whipple's disease. J Antimicrob Chemother. 2007 Sep;60(3):457-8. Epub 2007 Jul 10. | CrossRef | PubMed |

Boulos A, Rolain JM, Raoult D. Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. Antimicrob Agents Chemother. 2004 Mar;48(3):747-52. | CrossRef | PubMed | PMC |

Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic Tropheryma whipplei Clinical Presentation of 142 Patients with infections diagnosed or confirmed in a reference center. Medicine 2010; (89): 337-345. | CrossRef | PubMed |

Desnues B, Al Moussawi K, Fenollar F. New insights into Whipple’s disease and Tropheryma whipplei infections. Microbes and Infection 2010; (12) 1102-1110. | CrossRef | PubMed |

Lagier JC, Fenollar F, Lepidi H, Raoult D. Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease. J Antimicrob Chemother. 2010 Sep;65(9):2005-12. | CrossRef | PubMed |

Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. Gastroenterology. 2010 Feb;138(2):478-86; quiz 11-2. Epub 2009 Oct 29. | CrossRef | PubMed |

Bonhomme CJ, Renesto P, Desnues B, Ghigo E, Lepidi H, Fourquet P, Fenollar F, Henrissat B, Mege JL, Raoult D. Tropheryma whipplei glycosylation in the pathophysiologic profile of Whipple's disease. J Infect Dis. 2009 Apr 1;199(7):1043-52. | CrossRef | PubMed |

Gorvel L, Al Moussawi K, Ghigo E, Capo C, Mege JL, Desnues B. Tropheryma whipplei, the Whipple’s disease bacillus, induces macrophage apoptosis through the extrinsic pathway. Cell Death Dis. 2010 Apr 8;1:e34. | CrossRef | PubMed | PMC |

Koligi K, Mertz D, Benz D, Vogt T, Bloemberg GV, Winter L, Tyndall A, Battegay M, Walker UA. Of bugs and joints : Oligoarthritis caused by Tropheryma whipplei. Internist (Berl). 2011 Jul;52(7):884-888. | CrossRef | PubMed |

Jackuliak P, Koller T, Baqi L, Plank L, Lasabova Z, Minarik G, Payer J. Whipple’s Disease Generalized Stage. Dig Dis Sci 2008; (53):3250–3258. | CrossRef | PubMed |

Fenollar F Mediannikov O, Socolovschi C, Bassene H, Diatta G, Herve R et al. Tropheryma whipplei bacteremia during fever in rural West Africa. Clinical Infectious Diseases 2010; (5):515–521. | CrossRef | PubMed |

Rolain JM, Fenollar F, Raoult D. False positive PCR detection of Tropheryma whipplei in the saliva of healthy people, BMC Microbiology 2007; (7):48. | CrossRef | PubMed | PMC |

Fenollar F, Laouira S, Lepidi H, Rolain JM, Raoult D. Value of Tropheryma whipplei Quantitative Polymerase Chain Reaction Assay for the Diagnosis of Whipple Disease: sefulness of Saliva and Stool Specimens for First-Line Screening Clinical Infectious Diseases 2008; (47):659–67. | CrossRef | PubMed |

Tran H. Reversible hypothyroidism and Whipple's disease, BMC Endocrine Disorders 2006; (6):3. | CrossRef | PubMed | PMC |

Hansen A, Mereles D. Cardiac complications in Whipple’s disease, European Journal of Echocardiography 2008; (9): 426–427. | CrossRef | PubMed |

Misbah SA, Ozols B, Franks A, Mapstone N. Whipple's disease without malabsorption: new atypical features. QJM. 1997 Dec;90(12):765-72. | PubMed |

Ratnaike R. Whipples disease. Postgrad Med J 2000;(76):760-766. | CrossRef | PubMed | PMC |

Maiwald M, Relman D. Whipple’s Disease and Tropheryma whippelii: Secrets Slowly Revealed. Clinical Infectious Diseases 2001; (32):457–63. | PubMed |

Panegyres PK, Edis R, Beaman M, Fallon M. Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis. QJM. 2006 Sep;99(9):609-23. Epub 2006 Aug 11. | CrossRef | PubMed |

Müller C, Petermann D, Stain C, Riemer H, Vogelsang H, Schnider P, Zeiler K, Wrba F. Whipple's disease: comparison of histology with diagnosis based on polymerase chain reaction in four consecutive cases. Gut. 1997 Mar;40(3):425-7. | PubMed | PMC |

Knaapen HK, Barrera P. Therapy for Whipple's disease. J Antimicrob Chemother. 2007 Sep;60(3):457-8. Epub 2007 Jul 10. | CrossRef | PubMed |

Fredricks D, Relman D. Localization of Tropheryma whippelii rRNA in Tissues from Patients with Whipple?s Disease. The Journal of Infectious Diseases 2001;(183):1229?37. | CrossRef | PubMed |

La Scola B, Fenollar F, Fournier P, Altwegg M, Mallet M, Raoult D. Description of Tropheryma whipplei gen. nov sp. nov., the Whipple’s disease bacillus. International Journal of Systematic and Evolutionary Microbiology. 2001; (51): 1471–1479. | PubMed |

Panegyres P. Diagnosis and management of Whipples diasease of the brain. Pract Neurol 2008; (8): 311–317. | CrossRef | PubMed |

Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A. Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii). Appl Environ Microbiol. 1998 Feb;64(2):760-2. | PubMed | PMC |

Elkins C, Shuman T, Pirolo J. Cardiac Whipple’s disease without digestive symptoms. Ann Thorac Surg. 1999; (67):250–251. | CrossRef | PubMed |

Desnues B, Ihrig M, Raoult D, Mege JL. Whipple's disease: a macrophage disease. Clin Vaccine Immunol. 2006 Feb;13(2):170-8. | CrossRef | PubMed | PMC |

Kramer L, Manschot T, Barendregt J , Smit J. Whipple’s disease often a late diagnosis and a rare cause of nephropathy. NDT Plus 2009; (2): 55–58

Fenollar F, Lepidi H, Raoult D, Whipple’s Endocarditis Review of the Literature and Comparisons with Q Fever Bartonella Infection, and Blood Culture–Positive Endocarditis. Clinical Infectious Diseases. 2001; (33): 1309–16. | CrossRef | PubMed |

Di Sabatino A, Vidali F, Cazzola P, Marchese A, Biancheri P, Biagi F, Corazza GR. Splenic hypofunction in Whipple's disease. Am J Gastroenterol. 2009 Oct;104(10):2641-3. | CrossRef | PubMed |

Mahnel R, Kalt A, Ring S, Stallmach A, Strober W, Marth T. Inmunosuppresive therapy in Whipples disease patients in associated with the appearance of gastrointestinal manifestations. Am J Gastroenterol. 2005; (100):1167-1173. | CrossRef | PubMed |

Fenollar F, Raoult D. Infection: How should classic Whipple disease be managed? Nat Rev Gastroenterol Hepatol. 2010 May;7(5):246-8. | CrossRef | PubMed |

Basagiannis C, Panagoulias G, Tentolouris N, Basoukeas S, Sambaziotis D, Spiros L. Whipple Disease. Southern Medical Journal. Apr 2010; (103): 353-356. | CrossRef | PubMed |

Panegyres P, Jonathan F, Fallon M, Connor C. The Amnesic Syndrome of Primary Whipple Disease of the Brain. Cog Behav Neurol. 2010; (23):49–51. | CrossRef | PubMed |

Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol. 2009 May 7;15(17):2078-80. | CrossRef | PubMed | PMC |

Baisden B, Lepidi H, Raoult D, Argani P, Yardley JH, Dumler J. Diagnosis of Whipple Disease by Immunohistochemical Analysis. Am J Clin Pathol 2002; (118):742-748. | PubMed |

Desnues B, Raoult D, Mege JL. IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease. J Immunol 2005;(175):4575-4582. | PubMed |

Moos V, Kunkel D, Marth T, Feurle GE, LaScola B, Ignatius R, Zeitz M, Schneider T. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease. J Immunol. 2006 Aug 1;177(3):2015-22. | PubMed |

Feurle GE, Moos V, Schinnerling K, Geelhaar A, Allers K, Biagi F, Bläker H, Moter A, Loddenkemper C, Jansen A, Schneider T. The immune reconstitution inflammatory syndrome in whipple disease: a cohort study. Ann Intern Med. 2010 Dec 7;153(11):710-7. | PubMed |

Dutly F, Altwegg M. Whipple's disease and "Tropheryma whippelii". Clin Microbiol Rev. 2001 Jul;14(3):561-83. | CrossRef | PubMed | PMC |