Whipple's Disease

Whipple disease is a rare, infectious disorder characterized by weight loss, diarrhea, and joint pains. The syndrome was described by George Hoyt Whipple in 1907,^[1] and the causative organismTropheryma whipplei, was first seen in tissue samples from patients in 1961 and further identified in 1992.^[2]

Other Names

Intestinal Lipodystrophy

Signs and Symptoms

Whipple disease is a disorder that affects many systems in the body. It is primarily seen in middle-aged white men. Symptoms of the disease are listed in the following table:

Joint pains are often the first symptom that occur in this disease followed by diarrhea and abdominal pain days to months later. Other symptoms may occur depending on which organ systems are involved. The most common organ systems are shown in the table below:

Although the gastrointestinal tract is involved in virtually 100% of people, not everyone will have symptoms related to that organ system. The illness can sometime present in unusual ways making it difficult to diagnose.

Whipple disease can often have a chronic, relapsing course and the T. whipplei organism may persist in the body for long periods of time even after a prolonged course of antibiotics.^[3]

Causes

Whipple disease is caused by a bacterium called Tropheryma whipplei,^[4] also spelled in medical literature as Tropheryma whippelii. ^[5] The organism is difficult to grow in standard culture media in the laboratory and was not fully identified until 1992.^[2]

The organism appears to be found in the environment. One study identified it in waste water in Germany.^[6] However, it's natural habitat is unknown.

There is also evidence that in order to cause disease, a person infected with T. whipplei must also have a very specific abnormality in their immune system.

Diagnosis

The diagnosis of Whipple disease is usually made by demonstrating the organism in a sample of tissue obtained from a biopsy. The most common site for this procedure is the gastrointestinal tract, where the organism can be seen in most cases in a biopsy from the small intestines. Advanced techniques such as electron microscopy or polymerase chain reaction testing need to be done on biopsied tissue to confirm the diagnosis.

Treatment

Whipple disease is treated with antibiotics for prolonged periods of time. There are no randomized, controlled trials of different antibiotic regimens upon which to base recommendations. Based on observational studies, the treatment with the most success in improving symptoms and preventing recurrences is initial therapy with penicillin given by vein plus streptomycin given by injection into the muscle for two weeks, followed by trimethoprim-sulfamethoxazole given by mouth for one year. Ceftriaxone can be substituted for the initial penicillin and streptomycin.

One year of therapy is necessary to prevent recurrence of the syndrome. Prior studies have shown that if symptoms do recur after initial treatment, involvement of the central nervous system is likely and this can lead to severe disease and death.

Prevention

Since the method of spread of T. whipplei is unknown, specific recommendation to prevent spread of the microbe cannot be given. Research is ongoing as to how Whipple disease is spread.

Chances of Developing Whipple Disease

Whipple disease appears to occur primarily in white people in their mid-fifties and sixties. It occurs eight times more often in men than in women.

A specific genetic susceptibility to the illness is suggested by the fact that about 30% of people with Whipple disease have a specific abnormality in their T-cells, which are white blood cells that function in immunity.^[7]

How Whipple Disease is Spread

It is not clear how the bacterium that causes Whipple disease is spread. There is no evidence for person to person transmission. It has been found in waste water, suggesting that the microbe might be excreted in the stool of people who carry the infection.^[6]

Because virtually all people who have Whipple disease have evidence of involvement of the gastrointestinal tract, it is thought that people acquire the causative organism by mouth. The highest concentration of microbes is typically found in the small intestines.

T. whipplei has been found in people who have no signs of Whipple disease. Whether this suggests that the organism can normally be found in the gastrointestinal tract of healthy people (a commensal organism) or whether these people were infected but did not have the necessary genetic predisposition (and hence no illness) is not known.^{[8] [9]}

Related Problems

Complications

Whipple disease can involve the heart and the central nervous system. In the heart, it can lead to endocarditis or infection of the heart valves. It can also lead to infection of the heart muscle (myocarditis) or the covering of the heart (pericarditis). Involvement of the central nervous system can lead to severe illness with loss of memory, seizures, dementia, and death.

Expected Outcome

Generally, antibiotic treatment to destroy the bacteria that caused the disease results in relief of symptoms. However, the disorder may be persistent despite sustained treatment with antibiotics. Relapses are frequent. With treatment, the disorder can be cured. Untreated, Whipple's disease is fatal.

References

1. ↑ Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Johns Hopkins Hosp Bull. 1907;18:382-91.
2. ↑ ^{2.0 2.1} Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992;327:293–301. Abstract
3. ↑ Feurle GE, Marth T. An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole. Dig Dis Sci. 1994 Aug;39(8):1642-8. Abstract
4. ↑ La Scola B, Fenollar F, Fournier PE, Altwegg M, Mallet MN, Raoult D. Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple's disease bacillus. Int J Syst Evol Microbiol. 2001 Jul;51(Pt 4):1471-9. Abstract | PDF
5. ↑ Moore JE, Millar BC. Spelling of emerging pathogens. (Letter) Emerg Infect Dis. 2005:11(11);1796-7. Full Text | PDF
6. ↑ ^{6.0 6.1} Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A. Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii). Appl Environ Microbiol. 1998 Feb;64(2):760-2. Abstract | Full Text | PDF
7. ↑ Feurle GE, Dörken B, Schöpf E, Lenhard V. HLA B27 and defects in the T-cell system in Whipple's disease. Eur J Clin Invest. 1979 Oct;9(5):385-9. Abstract
8. ↑ Street S, Donoghue HD, Neild GH. Tropheryma whippelii DNA in saliva of healthy people. Lancet. 1999; 354:1178-9. Abstract
9. ↑ Maiwald M, von Herbey A, Persing DH, et al. Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple disease. Ann Intern Med 2001; 134:115-9. Abstract | PDF

External Links

National Digestive Diseases Information Clearinghouse: Whipple Disease

National Organization for Rare Disorders (NORD): Whipple Disease