Whipple disease is a rare disease resulting from bacterial infection that leads to inadequate absorption of nutrients (malabsorption) from the intestine. It is believed to result from infection with bacteria known as Tropheryma whippelii. The infection usually involves the small intestine, but over time, the disease may affect various parts of the body, including the heart, lungs, brain, and eyes.
The major symptoms of Whipple disease include abdominal pain after eating, joint pain, bouts of diarrhea, cough, chest pain, general weakness, and night sweats. Typically there is fat present in the stool (steatorrhea). Weight loss may occur because of a profound lack of appetite (anorexia). Anemia may result due to insufficient levels of iron, and pain may occur in several widely scattered joints (polyarthritis).
Other symptoms of Whipple disease may include: abnormally enlarged lymph nodes that are firm but usually not tender, an abnormally enlarged spleen (splenomegaly), increased color (pigmentation) of the skin, a decrease in blood pressure (hypotension), and abnormally high fevers that come and go. Some people with this disorder may experience a decrease in intellectual abilities, and an impairment of memory, judgment, and/or abstract thought. Occasionally, the loss of intellectual skills progresses to dementia. Eye movements may be impaired and uncontrolled muscular movements (myoclonus) may occur when Whipple disease has affected the brain or central nervous system. (For more information on this disorder, choose “Myoclonus” as your search term in the Rare Disease Database.)
The central nervous system is affected in the later stages of untreated Whipple disease. Symptoms of neurological involvement may include hearing loss, persistent ringing in the ears (tinnitus), and impairment of vision. (For more information on this disorder, choose “Tinnitus” as your search term in the Rare Disease Database.) In rare cases of this disorder, the heart may be affected resulting in congestive heart failure and/or inflammation of the membranes that surround the heart (pericarditis).
If Whipple disease remains untreated and malabsorption from the small intestine becomes worse, the affected person may have low levels of circulating calcium and magnesium in the blood (hypokalemia and hypomagnesemia) resulting in muscle cramps, convulsions, and twitching (tetany). Damage to the nerves, especially those of the arms and legs (peripheral neuropathy) may also occur. (For more information on these disorders, choose “Neuropathy, Peripheral” as your search term in the Rare Disease Database.)
Whipple disease is caused by a rod-shaped bacterium called Tropheryma whippelii. This bacterium was first identified in 1991/92. Its natural habitats are unknown, but it appears likely that infection occurs by way of an environmental source and that the bacteria are introduced into the body through the mouth (peroral).
Whipple disease affects more males than females in a ratio of approximately 4 to 1. The symptoms of this disorder typically begin between the ages of thirty and sixty years. The age range of those affected is thought to be between 30 and 80, with the median age at time of diagnosis being 56 years. Most of the cases of Whipple disease have been diagnosed among Europeans and Americans of European parentage. In Germany, the disease incidence has been estimated at 0.4 per million population per year. A few cases have been reported among American Indians and Americans of African descent. In 2004, for the first time, a case of Whipple disease was reported in Japan.
The standard diagnostic approach is to study a tissue sample (biopsy) from the small intestine. Blood testing can determine whether anemia is present. Confirmation of diagnosis can be achieved either by electron microscopy or by a test known as polymerase chain reaction (PCR) analysis, which detects the DNA of T. whippelii.
If not treated, Whipple disease can become life-threatening. It can be cured, however, with antibiotics. Various types and combinations of antibiotics have been used. Relapses may occur, either during therapy or after it has been completed. For that reason, antibiotic therapy may be extended over a long period of time (up to a year or longer). One combination of antibiotics considered to be effective is trimethoprim-sulfamethoxazole, but there are also several alternatives. If symptoms reappear during therapy, a change in the antibiotic regimen may be needed. Complete healing may require as long as two years.
Some patients with severe intestinal malabsorption caused by Whipple disease may need the intravenous administration of fluids and electrolytes. Other patients may require iron, folate supplements, vitamin D, and calcium. Since most patients with this disorder suffer from malnutrition, the recommended diet is usually high in calories and protein. Both diet and antibiotics must be monitored regularly by a physician.
While the symptoms of WD may improve rapidly with long-term antibiotic therapy, biopsy may reveal bacteria in the small intestine for up to two years. Whipple's disease has been completely reversed by antibiotic therapy. The absence of bacilliform (rod shaped bacteria) in a biopsy sample of the small bowel typically suggests remission and possible cure.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
von Herbay A. Whipple Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:297-98.
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:301.
Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:737.
Yamada T, Alpers DH, Owyang C, et al. Eds. Textbook of Gastroenterology. 2nd ed. J. B. Lippincott Company. Philadephia, PA; 1995:1634-40.
Mandell GL, Bennett JE, Dolan R., eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone Inc. New York, NY; 1995:1030-32.
Muller SA, Vogt P, Altwegg M, et al. Deadly carousel or difficult interpretation of new diagnostic tools for Whipple’s disease: case report and review of the literature. Infection. 2005;33:39-42.
Mahnel R, Marth T. Progress, problems and perspectives in diagnosis and treatment of Whipple’s disease. Clin Exp Med. 2004;4:39-42.
Moreillon P, Que YA. Infective endocarditis. Lancet. 2004;363:139-49.
Louis ED. Whipple disease. Curr Neurol Neurosci Rep. 2003;3:470-75.
Khan A, Lightmen S. The eye in gastrointestinal disease. Hosp Med. 2003;64:548-51.
Holden W, Orchard T. Wordsworth P. Enteropathic arthritis. Rheum Dis Clin North Am. 2003;29:513-30.
Hill Gaston JS, Lillicrap MS. Arthritis associated with enteric infection. Best Pract Res Clin Rheumatol. 2003;17:219-39.
Nelson JW, White ML, Zhang Y, et al. Proton Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging of Central Nervous System Whipple Disease. J Comput Assist Tomogr. 2005;29:320-322.
Mahnel R, Kalt A, Ring S, et al. Immunosuppressive therapy in Whipple’s disease patients is the association with the appearance of gastrointestinal manifestations. Am J Gastroenterol. 2005;100:1167-73.
Matthews BR, Jones LK, Saad DA, et al. Cerebellar ataxia and central nervous system whipple disease. Arch Neurol. 2005;62:618-20.
Rossi T, Haghighipour R, Haghighi M, et al. Cerebral Whipple’s disease as a cause of reversible dementia. Clin Neurol Neurosurg. 2005;107:258-61.
Friedmann AC, Perera GK, Jayaprakasam A, et al. Whipple’s disease presenting with symmetrical panniculitis. Br J Dermatol. 2004;151:907-11.
FROM THE INTERNET
Whipple’s Disease. National Digestive Diseases Information Clearinghouse (NDDIC). September 2004. 3pp.
European Research Project on Whipple’s Disease.
Feurle GE. Whipple’s Disease. Orphanet. Update: December 2004. 3pp.
Whipple’s Disease. Pennsylvania State University: Milton S. Hershey Medical Center, College of Medicine. nd. 2pp.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100