Whipple's Disease

What Is Whipple's Disease? What Causes Whipple's Disease?

Whipple's disease is a rare infectious disease caused by a bacteria called tropheryma whipplei. This intestinal disease is named after George Whipple, who discovered the bacteria in 1907.

Tropheryma whippeli, which was reported in the year 2000 to have been grown in the laboratory, opened the way for the development of a simple blood test to diagnose the disease.

Fortunately, it can be treated with antibiotics. Some patients relapse and need long-term, even life-long, treatment. Whipple's can be deadly.

In the United States, Whipple's disease affects only one in a million people each year. In developing countries, it is more prominent and can especially affect children who live in areas where the sanitation system is poor. Doctors discovered that nearly 44 percent of children in Senegal were confirmed to have the causative bacteria in their stools, and most of them were between the ages of 4 and 10.

According to Medilexicon's medical dictionary:

Whipple's Disease is a rare condition characterized by steatorrhea, frequently generalized lymphadenopathy, arthritis, fever, and cough; many macrophages are found in the jejunal lamina propria; caused by Tropheryma whippleii. May lead to progressive malnutrition, dementia, and if untreated, death.

Whipple's disease is significantly more common in men, with 87% of the patients being male. In some countries the rate of women receiving a diagnosis of Whipple's disease has increased in recent years. It occurs predominantly in those of Caucasian ethnicity, suggesting a genetic predisposition in that population.

What are the symptoms of Whipple's Disease?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

One of the most common signs of the disease is weight loss. Weight loss is caused by malabsorption, which means the body cannot absorb nutrients through the bloodstream. Some other symptoms of the disease are diarrhea, stomach pain, weakness, fatigue, anemia and a darkening or graying of skin exposed to the sun.

Darkening of the skin occurs in almost half of cases; some also have skin nodules. Various eye problems, such as uveitis, may occur, which is typically associated with deteriorating vision and pain in the affected eye. Endocarditis (infection of the heart valve) has been reported in a small number of cases, sometimes in people with no other symptoms of Whipple's disease. This is typically noticed as breathlessness and leg swelling due to fluid accumulation as the heart is unable to pump fluid through the body.
Whipple's disease, if allowed to progress, can affect the central nervous system. If that occurs, a person begins to experience declining intellectual abilities, insomnia, hearing loss and eventually dementia or death.

What are the causes of Whipple's Disease?

Whipple's disease is caused by the organism Tropheryma whippeli. It causes a severe infection in the lining of the small intestine, which can spread to the heart, lung, brain, joints, and eyes. It can affect any system of the body, but occurs most often in the small intestine.

The disease causes lesions on the wall of the small intestine and thickening of the tissue. The villi, tiny, finger-like protrusions from the wall that help absorb nutrients, are destroyed.

Those individuals most susceptible to the acquisition of the disease, are those with decreased ability to perform intracellular degredation of ingested pathogens or particles, particularly in the macrophages.

Diagnosing Whipple's Disease

The diagnosis of Whipple's disease is made by demonstrating the characteristic lesions in any affected tissue. This is best accomplished via small bowel biopsy performed during upper endoscopy. Endoscopic findings of Whipple's disease include areas of thickened folds with the typical granular, yellow-white shaggy covering. A biopsy specimen revealing infiltration of the lamina propria of the small bowel with PAS-positive macrophages containing gram-positive, AFB-negative bacilli and lymphatic dilation is specific and diagnostic of Whipple disease.

The polymerase chain reaction (PCR) method has been used to amplify DNA unique to Tropheryma whippeli extracted from various tissue samples of patients with Whipple disease. PCR method can be used to confirm the diagnosis of Whipple's disease when the diagnosis cannot be confirmed histologically. It is highly sensitive and specific and is useful in suspicious, inconclusive cases.

It is suggested that a negative PCR result after therapy might predict a low clinical relapse rate, whereas a persistently positive PCR result despite treatment may be associated with disease recurrence. Since most, if not all, patients with Whipple's disease have central nervous system infection, but only some develop clinical or radiologic evidence of the disease and that PCR analysis of the cerebrospinal fluid can be added to the diagnostic evaluation to detect those with cerebral Whipple's disease.

What are the treatment options for Whipple's Disease?

For many years Whipple's disease was considered a fatal primary metabolic disorder.

Antibiotics now are the mainstay of treatment, often providing dramatic life-saving improvement of symptoms. Antibiotic regimens include penicillin with or without streptomycin, erythromycin, ampicillin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.

Relapses are common and can occur months or even years after initial treatment. Many of the relapses occur in the central nervous system, and thus, antibiotics should have adequate blood-brain barrier penetration.

Because of the rarity of the disease, controlled and prospective evaluations of different treatment regimens will probably never be possible. Recommendations are based on case reports, retrospective reviews, and antibiotic characteristics.

Treatment with trimethoprim-sulfamethoxazole for 6 to 12 months is recommended both for initial therapy and for relapses of the disease. Other antibiotic regimens reported may be associated with a higher relapse rate and are considered to be second-line agents.

With effective treatment, the small intestinal mucosa reverts toward normal. Bacilli disappear within a few days, and after 1 to 2 months, only dying organisms may be seen. The number of PAS-positive macrophages decreases, and the mucosa regains its normal villous architecture. For some patients, however, it may take years to obtain a normal histologic appearance.

Other considerations, not specific for Tropheryma whippeli infection, are extremely important to patient outcome. Proper fluid and electrolyte replacement in patients with intestinal malabsorption is vital. Iron or folate supplements may be required to correct anemia. Vitamin D, calcium, and magnesium may be necessary to maintain calcium homeostasis. Vitamin K is used to correct coagulopathy. The diet should be appropriately high in calories, protein, and other vitamins because most of the patients are malnourished. Long-term hyperalimentation is rarely indicated.

Immunologic studies have shown reduced production of interleukin-12 and interferon-gamma in patients with Whipple's disease. It is not yet determined whether the immunoregulatory defect is a primary or secondary result of the infection. The addition of interferon-gamma may be an option in the treatment of patients with refractory Whipple's disease but further studies are needed to clarify benefit of their therapy.