Information on the following diseases can be found in the Related Disorders section of this report:

• Crohn's Disease
• Ulcerative Colitis
• Primary Sclerosing Cholangitis
• Chronic Erosive Gastritis
• Irritable Bowel Syndrome
• Intestinal Pseudoobstruction
• Giant Hypertrophic Gastritis
• AIDS

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.

Symptoms of the following disorders can be similar to those of Whipple disease. Comparisons may be useful for a differential diagnosis:

Crohn's disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. Symptoms may include vomiting, fever, night sweats, loss of appetite, general weakness, and waves of abdominal pain and discomfort. Diarrhea and bleeding from the rectum are common in people who have Crohn's disease. Weight loss is also common. The symptoms of this disorder can be difficult to manage and diagnosis is often delayed. (For information on this disorder, choose "Crohn's Disease" as your search term in the Rare Disease Database.)

Ulcerative colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and urgency (tenesmus). Weight loss and a decrease in appetite are also associated with ulcerative colitis. (For more information on this disorder, choose "Ulcerative Colitis" as your search term in the Rare Disease Database.)

Primary sclerosing cholangitis is a rare collagen disorder involving inflammation and blockage of the bile duct, liver ducts, and gallbladder. Symptoms of this disorder include abdominal pain, loss of appetite, nausea, vomiting, and/or weight loss. Later symptoms may include a yellow discoloration to the skin (jaundice), fever, chills, and/or itching of the skin. Bacterial infections may be associated with bile duct blockages of primary sclerosing cholangitis. (For more information on this disorder, choose "Primary Sclerosing Cholangitis," as your search term in the Rare Disease Database.)

Chronic erosive gastritis is an inflammatory digestive disorder characterized by multiple lesions in the mucus lining of the stomach. Symptoms of this disorder may include burning or a heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of chronic erosive gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose "Chronic Erosive Gastritis" as your search term in the Rare Disease Database.)

Irritable bowel syndrome, also known as spastic colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with irritable bowel syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose "Irritable Bowel Syndrome" as your search term in the Rare Disease Database.)

Intestinal pseudoobstruction is a gastrointestinal disorder characterized by a lack of motility of the intestine. This condition resembles a true obstruction although there is no evidence of any physical obstruction. Symptoms may include constipation, colicky pain, vomiting, and weight loss. Intestinal pseudoobstruction may also affect speech, muscle activity, and the nervous system. (For more information on this disorder, choose "Intestinal Pseudoobstruction, Intestinal" as your search term in the Rare Disease Database.)

Giant hypertrophic gastritis is a chronic disorder characterized by the presence of large, coiled ridges or folds, in the inner wall of the stomach. Symptoms include abdominal pain or discomfort and tenderness in the upper middle region of the abdomen. Other symptoms may include a profound loss of appetite, nausea, vomiting, and diarrhea. (For more information on this disorder, choose "Giant Hypertrophic Gastritis" as your search term in the Rare Disease Database.)

Acquired immune deficiency syndrome (AIDS) is an immunosuppressive disorder caused by infection with the human immunodeficiency virus (HIV). The immune deficiency is a result of a viral infection and the destruction of specific T cells. Initially HIV infection is characterized by a period without symptoms. This may be followed by the development of swollen lymph nodes (lymphadenopathy). Eventually most people with acquired immune deficiency syndrome experience a progression of symptoms that occur as a result of a compromised immune system. When a person with AIDS has an intestinal infection with Mycobacterium avium intracellulare, the symptoms may be confused with those of Whipple disease. (For more information on this disorder, choose "AIDS" as your search term in the Rare Disease Database.)

Diagnosis
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.

Treatment
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: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

TEXTBOOKS
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.

REVIEW ARTICLES
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.

JOURNAL ARTICLES
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.
http://digestive.niddk.nih.gov/ddiseases/pubs/whipple/

European Research Project on Whipple's Disease.
www.eurice.info/typo3sites/index.php?id=149

Feurle GE. Whipple's Disease. Orphanet. Update: December 2004. 3pp.
www.orpha.net/patho/GB/uk-Whipple.html

Whipple's Disease. Pennsylvania State University: Milton S. Hershey Medical Center, College of Medicine. nd. 2pp.
www.hmc.psu.edu/healthinfo/uz/whipple.htm