eMedicine Specialties > Gastroenterology > Intestine

Whipple Disease: Differential Diagnoses & Workup

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
Contributor Information and Disclosures

Updated: Aug 14, 2008

Differential Diagnoses

Abdominal Angina
Celiac Sprue
Malabsorption
Sprue, Tropical

Other Problems to Be Considered

AIDS-related complex
Endocarditis, bacterial and nonbacterial
Human immunodeficiency virus (HIV) enteropathy
Macroglobulinemia
Mycobacterium avium intracellulare infection
Abetalipoproteinemia and hypobetalipoproteinemia

Workup

Laboratory Studies

  • Basic laboratory studies that suggest the presence of malabsorption may be useful screening tests, as follows:
    • Sudan stain of stool
    • Serum carotene
    • Serum albumin
    • Prothrombin time
  • The definitive test for the presence of malabsorption is the 72-hour fecal fat determination.
  • Abnormalities in any of these laboratory test results suggest that malabsorption is present, but they are not specific for Whipple disease.

Imaging Studies

  • Imaging studies, such as a CT scan and a small-bowel series, may suggest the presence of malabsorption, but these imaging studies are not specific for Whipple disease.
  • Brain MRI may demonstrate T1, T2, and fluid-attenuated inversion recovery abnormalities in the cerebellar peduncles, vermis, medulla, and foci of enhancement in the subcortical white matter, but these abnormalities are not pathognomonic for Whipple disease.

Other Tests

  • No tests are specific for diagnosis except determining the presence of T whippelii DNA through PCR.  
    • This test is not available universally. PCR currently is performed only at a few centers, including the Mayo Clinic and StanfordUniversity.
    • Availability and cost are prohibitive to obtaining this test. Check for availability with the medical laboratory and for cost approval with each hospital or office laboratory used by the practice.
    • IgG antibody for T whippelii should not be used diagnostically, as up to 70% of control subjects demonstrate the antibody. IgM antibody is more specific but not easily available.

Procedures

  • Biopsy of the appropriate tissue is essential for establishing a diagnosis.
    • These tissues may include small bowel, brain, endocardial, and synovial.
    • Biopsies of tissue samples from the small bowel show expanded villi containing macrophages staining positive with periodic acid-Schiff stain. This finding leads to electron microscopy and then DNA testing for T whippelii.

Histologic Findings

For intestinal disease, a small-bowel biopsy may show the lamina propria of the small bowel full of periodic acid-Schiff–positive macrophages. Endocardial, brain, or synovial biopsies may show similar changes for Whipple endocarditis, CNS Whipple disease, or synovial Whipple disease, respectively. The presence of T whippelii by PCR in patients who are clinically symptomatic is pathognomonic for the disease.

More on Whipple Disease

Overview: Whipple Disease
Differential Diagnoses & Workup: Whipple Disease
Treatment & Medication: Whipple Disease
Follow-up: Whipple Disease
References
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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].

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  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. 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].

  21. 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].

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

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Further Reading

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Keywords

Whipple disease, Whipple's disease, Tropheryma whippelii, T whippelii, intestinal lipodystrophy, WD, polyarthralgias, chronic diarrhea, Whipple disease with symptomatic CNS involvement, fever of unknown origin

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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.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal 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; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
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 and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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