Whipple Disease 

  • Author: Ingram M Roberts, MD, MBA; Chief Editor: Julian Katz, MD   more...
 
Updated: Dec 2, 2011
 

Background

Whipple disease is a systemic disease most likely caused by a gram-positive bacterium, Tropheryma whippelii.[1, 2] Although the first descriptions of the disorder described a malabsorption syndrome with small intestine involvement, the disease also affects the joints, CNS, and cardiovascular system. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse.

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Pathophysiology

The clinical manifestations of the disease are believed to be caused by infiltration of the various body tissues by T whippelii. The patient's immune system reacts by incorporating the organisms into tissue macrophages.

These macrophages can be easily observed infiltrating the tissues using conventional light microscopy. The macrophages are easily observed when periodic acid-Schiff stain is used for the histologic sections. However, positive periodic acid-Schiff–stained macrophages infiltrating body tissues are not pathognomonic for Whipple disease. These microphages also can be detected in infection due to Mycobacterium avium intracellulare, cryptococcosis, or other parasitic organisms (usually observed in patients who are immunosuppressed with HIV disease).[3, 4] Stains for fungal organisms and acid-fast bacilli are helpful in ruling out Whipple disease.

Diagnostic electron microscopy reveals coccobacillary bodies that represent the T whippelii organism. This is diagnostic because a positive polymerase chain reaction (PCR) for T whippelii will be present in the affected tissue.[5, 6, 7]

The malabsorption observed in the small bowel that is associated with this condition is believed to be secondary to the disruption of normal villous function due to infiltration of the lamina propria of the small bowel. Patients with arthralgias have been found to have the organism in the synovial tissues.[8] The organisms have been detected in the heart valves of patients with cardiac Whipple disease[9, 10] and in the CNS of patients with neurologic disease.[11] Rarely, the organism can be detected in the lungs of affected patients.[12] In short, although Whipple disease represents a systemic condition, only a few organ systems of the body are affected overtly.

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Epidemiology

Frequency

International

Whipple disease is extremely rare worldwide; only several hundred clinical cases have been reported, mostly from North America and western Europe. The disease appears to be associated with the human leukocyte antigen B27 (HLA-B27) haplotype.[13] The incidence has been estimated to be less than 1 per 1,000,000.[14]

Mortality/Morbidity

Untreated patients have a poor prognosis. The disease is almost universally fatal after 1 year in patients who do not receive the correct diagnosis and therapy.[15, 16, 17]

Race

Whipple disease is most common in white males and rarely is described in females.

Sex

Whipple disease is more predominant in males than in females, roughly 8-9:1.

Age

Whipple disease is usually observed in middle-aged and elderly persons (older than 40 y).

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Contributor Information and Disclosures
Author

Ingram M Roberts, MD, MBA  Associate Clinical Professor of Medicine, University of Connecticut School of Medicine; Program Director of Internal Medicine Residency, Vice Chairman, Department of Medicine, St Vincent's Medical Center

Ingram M Roberts, MD, MBA is a member of the following medical societies: American College of Gastroenterology, American College of Physician Executives, American College of Physicians, American Gastroenterological Association, American Medical Informatics Association, American Society for Gastrointestinal Endoscopy, and Association of Program Directors in Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Marco G Patti, MD  Professor of Surgery, Director, Center for Esophageal Diseases, University of Chicago Pritzker School of Medicine

Marco G Patti, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Surgeons, American Gastroenterological Association, American Medical Association, American Surgical Association, Association for Academic Surgery, Pan-Pacific Surgical Association, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Southwestern Surgical Congress, and Western Surgical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Noel Williams, MD  Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

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  2. Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple's disease. N Engl J Med. Mar 2 2000;342(9):620-5. [Medline].

  3. Dray X, Vahedi K, Delcey V, et al. Mycobacterium avium duodenal infection mimicking Whipple's disease in a patient with AIDS. Endoscopy. Feb 2007;39 Suppl 1:E296-7. [Medline].

  4. Patel SJ, Huard RC, Keller C, et al. Possible Case of CNS Whipple's Disease in an Adolescent With AIDS. J Int Assoc Physicians AIDS Care (Chic Ill). Jun 2008;7(2):69-73. [Medline].

  5. Ramzan NN, Loftus E Jr, Burgart LJ, et al. Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med. Apr 1 1997;126(7):520-7. [Medline].

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  8. O'Duffy JD, Griffing WL, Li CY, et al. Whipple's arthritis: direct detection of Tropheryma whippelii in synovial fluid and tissue. Arthritis Rheum. Apr 1999;42(4):812-7. [Medline].

  9. Celard M, de Gevigney G, Mosnier S, et al. Polymerase chain reaction analysis for diagnosis of Tropheryma whippelii infective endocarditis in two patients with no previous evidence of Whipple's disease. Clin Infect Dis. Nov 1999;29(5):1348-9. [Medline].

  10. Gubler JG, Kuster M, Dutly F, et al. Whipple endocarditis without overt gastrointestinal disease: report of four cases. Ann Intern Med. Jul 20 1999;131(2):112-6. [Medline].

  11. Gerard A, Sarrot-Reynauld F, Liozon E, et al. Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore). Nov 2002;81(6):443-57. [Medline].

  12. Kelly CA, Egan M, Rawlinson J. Whipple's disease presenting with lung involvement. Thorax. Mar 1996;51(3):343-4. [Medline].

  13. Dobbins WO 3rd. HLA antigens in Whipple's disease. Arthritis Rheum. Jan 1987;30(1):102-5. [Medline].

  14. Fenollar F, Puéchal X, Raoult D. Whipple's disease. N Engl J Med. Jan 4 2007;356(1):55-66. [Medline].

  15. Durand DV, Lecomte C, Cathebras P, et al. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore). May 1997;76(3):170-84. [Medline].

  16. Keinath RD, Merrell DE, Vlietstra R, et al. Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology. Jun 1985;88(6):1867-73. [Medline].

  17. Fleming JL, Wiesner RH, Shorter RG. Whipple's disease: clinical, biochemical, and histopathologic features and assessment of treatment in 29 patients. Mayo Clin Proc. Jun 1988;63(6):539-51. [Medline].

  18. Sheib JS. Whipple disease revisited. Radiographic features of a patient with 35 years of undiagnosed arthritis. J Clin Rheumatol. 2004;10:69-73.

  19. Matthews BR, Jones LK, Saad DA, et al. Cerebellar ataxia and central nervous system Whipple disease. Arch Neurol. Apr 2005;62(4):618-20. [Medline].

  20. Fenollar F, Nicoli F, Paquet C, Lepidi H, Cozzone P, Antoine JC, et al. Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis. BMC Infect Dis. Jun 15 2011;11:171. [Medline]. [Full Text].

  21. Süzer T, Demirkan N, Tahta K, et al. Whipple's disease confined to the central nervous system: case report and review of the literature. Scand J Infect Dis. 1999;31(4):411-4. [Medline].

  22. Ehrbar HU, Bauerfeind P, Dutly F, et al. PCR-positive tests for Tropheryma whippelii in patients without Whipple's disease. Lancet. Jun 26 1999;353(9171):2214. [Medline].

  23. Street S, Donoghue HD, Neild GH. Tropheryma whippelii DNA in saliva of healthy people. Lancet. Oct 2 1999;354(9185):1178-9. [Medline].

  24. Whistance RN, Elfarouki GW, Vohra HA, Livesey SA. A case of Tropheryma whipplei infective endocarditis of the aortic and mitral valves in association with psoriatic arthritis and lumbar discitis. J Heart Valve Dis. May 2011;20(3):353-6. [Medline].

  25. Swartz MN. Whipple's disease--past, present, and future. N Engl J Med. Mar 2 2000;342(9):648-50. [Medline].

 
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