Medscape is available in 5 Language Editions – Choose your Edition here.


Whipple Disease

  • Author: Ingram M Roberts, MD, MBA; Chief Editor: Julian Katz, MD  more...
Updated: Dec 29, 2015


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, central nervous system, and cardiovascular system. T whipplei infection is recognized to be a major cause of culture-negative endocarditis.[3] Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse.[4]



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).[5, 6] 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.[7, 8, 9]

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.[10] The organisms have been detected in the heart valves of patients with cardiac Whipple disease[11, 12] and in the CNS of patients with neurologic disease.[13] Rarely, the organism can be detected in the lungs of affected patients.[14] In short, although Whipple disease represents a systemic condition, only a few organ systems of the body are affected overtly.



The disease is believed to be due to a disordered host response to the bacterium T whippelii.[15] Of note, patients with human immunodeficiency virus (HIV) infection do not acquire the disease.

Data that suggest that T whippelii DNA may be found in patients who are asymptomatic.[16, 15]  One study revealed its presence in saliva in 35% of a sample of 40 healthy patients.[17]  This suggests that Whipple disease is a manifestation of an abnormal host response to a microorganism that may occur frequently in humans (perhaps in a similar manner to that observed with Helicobacter pylori).

To date, Koch's postulates have not been fulfilled completely (infection of an animal model and isolation of the organism from the animal). However, T whippelii bacteria have been grown successfully in HEL (a human fibroblast line) cells.[2]  The production of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies has been shown. The organism has been cultured from affected cerebrospinal fluid (CSF) and vitreous humor of patients with Whipple disease.



International statistics

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.[18] The incidence has been estimated to be less than 1 per 1,000,000.[19]

Race-, sex-, and age-related demographics

Whipple disease is most common in white males[15] and rarely is described in females (male-to-female ratio: approximately 8-9:1).

Whipple disease is usually observed in middle-aged[15] and elderly persons (older than 40 y).



If Whipple disease is untreated, the prognosis is poor, and mortality approaches 100% after 1 year in patients who do not receive the correct diagnosis and therapy.[20, 21, 22]

If this condition is treated for a full year, the prognosis usually is good. Clinical remission occurs in approximately 70% of patients.


Up to 30-40% of patients may relapse, and relapse appears to be more common in patients with central nervous system (CNS)–related Whipple disease.

A potential complication is a reaction or allergy to antibiotics that could require changing the antibiotic agent.

Contributor Information and Disclosures

Ingram M Roberts, MD, MBA Clinical Professor of Medicine (Adjunct), Temple University School of Medicine

Ingram M Roberts, MD, MBA is a member of the following medical societies: American College of Gastroenterology, American Association for Physician Leadership, American Gastroenterological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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

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, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

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 Surgical Association, American College of Surgeons, American Gastroenterological Association, American Medical 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, Western Surgical Association

Disclosure: Nothing to disclose.

  1. Relman DA, Schmidt TM, MacDermott RP, et al. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30. 327(5):293-301. [Medline].

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

  3. Herrmann MD, Neumayr A, Essig A, Spiess J, Merk J, Möller P, et al. Isolated Whipple's endocarditis: an underestimated diagnosis that requires molecular analysis of surgical material. Ann Thorac Surg. 2014 Jul. 98(1):e1-3. [Medline].

  4. Arnold CA, Moreira RK, Lam-Himlin D, De Petris G, Montgomery E. Whipple disease a century after the initial description: increased recognition of unusual presentations, autoimmune comorbidities, and therapy effects. Am J Surg Pathol. 2012 Jul. 36(7):1066-73. [Medline].

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

  6. 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). 2008 Jun. 7(2):69-73. [Medline].

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

  8. Marth T, Schneider T. Whipple disease. Curr Opin Gastroenterol. 2008 Mar. 24(2):141-8. [Medline].

  9. Schneider T, Moos V, Loddenkemper C, et al. Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar. 8(3):179-90. [Medline].

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

  11. 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. 1999 Nov. 29(5):1348-9. [Medline].

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

  13. 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). 2002 Nov. 81(6):443-57. [Medline].

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

  15. Marth T. Tropheryma whipplei , Immunosuppression and Whipple's disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex. Dig Dis. 2015. 33 (2):190-9. [Medline].

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

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

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

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

  20. 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). 1997 May. 76(3):170-84. [Medline].

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

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

  23. Cunningham S, Maulucci F, Zufferey P, Ribi C, Maillard MH. [Whipple's disease, when to think about it?] [French]. Rev Med Suisse. 2015 Sep 2. 11 (484):1582, 1584-6. [Medline].

  24. Marth T. Systematic review: Whipple's disease (Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Aliment Pharmacol Ther. 2015 Apr. 41 (8):709-24. [Medline].

  25. Ramos JM, Pasquau F, Galipienso N, et al. Whipple's disease diagnosed during anti-tumor necrosis factor alpha treatment: two case reports and review of the literature. J Med Case Rep. 2015 Jul 28. 9:165. [Medline].

  26. Gaude M, Tebib J, Puechal X. Atypical focal forms of Whipple's disease seen by rheumatologists. Joint Bone Spine. 2015 Jan. 82 (1):56-9. [Medline].

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

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

  29. 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. 2011 Jun 15. 11:171. [Medline]. [Full Text].

  30. 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].

  31. Compain C, Sacre K, Puéchal X, Klein I, Vital-Durand D, Houeto JL, et al. Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. Medicine (Baltimore). 2013 Nov. 92(6):324-30. [Medline].

  32. Yajima N, Wada R, Kimura S, Matsuzaki Y, Chiba D, Ebina Y, et al. Whipple disease diagnosed with PCR using formalin-fixed paraffin-embedded specimens of the intestinal mucosa. Intern Med. 2013. 52(2):219-22. [Medline].

  33. Moter A, Schmiedel D, Petrich A, Wiessner A, Kikhney J, Schneider T, et al. Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years' experience in a National Reference Laboratory. J Clin Microbiol. 2013 Nov. 51(11):3858-61. [Medline]. [Full Text].

  34. 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. 2011 May. 20(3):353-6. [Medline].

  35. Gunther U, Moos V, Offenmuller G, et al. Gastrointestinal diagnosis of classical Whipple disease: clinical, endoscopic, and histopathologic features in 191 patients. Medicine (Baltimore). 2015 Apr. 94 (15):e714. [Medline].

  36. Fenollar F, Lagier JC, Raoult D. Tropheryma whipplei and Whipple's disease. J Infect. 2014 Aug. 69 (2):103-12. [Medline].

  37. Vayssade M, Tournadre A, D'Incan M, Soubrier M, Dubost JJ. Immune reconstitution inflammatory syndrome during treatment of Whipple's disease. Joint Bone Spine. 2015 Mar. 82 (2):122-4. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.