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Whipple's disease
Last reviewed: 12.07.2025
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Whipple's disease is a rare systemic disease caused by the bacterium Tropheryma whippelii. The main symptoms of Whipple's disease are arthritis, weight loss, and diarrhea. Diagnosis is made by small bowel biopsy. Treatment of Whipple's disease involves taking trimethoprim-sulfamethoxazole for at least 1 year.
Whipple disease predominantly affects white individuals aged 30–60 years. Although multiple organs are affected (e.g., heart, lung, brain, serous cavities, joints, eyes, gastrointestinal tract), the small intestinal mucosa is almost always involved. Patients may have subtle defects in cell-mediated immunity that predispose to T. whippelii infection. Approximately 30% of patients have HLAB27.
What causes Whipple's disease?
In 1992, the bacterial nature of Whipple's disease was established (Relman, Schmidt, MacDermott, 1992). Gram-positive actinomycetes Tropheryna whippelii were identified as the infectious agent. These small Gram-positive bacteria are found in large quantities in the mucous membrane of the small intestine and other organs during the active phase of the disease and disappear after intensive antibacterial treatment. A predisposing factor to the development of the disease is a dysfunction of the immune system of various origins.
Symptoms of Whipple's Disease
The clinical features of Whipple disease vary depending on the organ systems affected. Arthritis and fever are usually the first signs. The intestinal symptoms of Whipple disease (eg, watery diarrhea, steatorrhea, abdominal pain, anorexia, weight loss) usually appear later, sometimes years after the initial complaints. Profuse or occult intestinal bleeding may occur. Severe malabsorption may appear and be diagnosed in patients late in the clinical course. Other examination findings include increased skin pigmentation, anemia, lymphadenopathy, chronic cough, polyserositis, peripheral edema, and CNS features.
Diagnosis of Whipple's disease
The diagnosis may be unreliable in patients with no apparent gastrointestinal symptoms. Whipple's disease should be suspected in middle-aged whites with arthritis, abdominal pain, diarrhea, weight loss, or other signs of malabsorption. In such patients, upper gastrointestinal endoscopy with small bowel biopsy is required; the intestinal lesions are specific and diagnostic. The most significant and persistent changes affect the proximal small bowel. Light microscopy allows visualization of PAS-positive macrophages, which distort the villous architecture. Gram-positive, acid-stain-negative bacilli (T. whippelii) are seen in the lamina propria and macrophages. Confirmation by electron microscopy is recommended.
Whipple's disease must be differentiated from Mycobacterium avium-intracellulare (MAI), an intestinal infection that has similar histologic features. However, MAI stains positive with acid stain. Polymerase chain reaction may be helpful to confirm the diagnosis.
Diagnosis of Whipple's disease
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Treatment of Whipple's disease
Without treatment, Whipple's disease is progressive and can be fatal. Various antibiotics (eg, tetracycline, trimethoprim-sulfamethoxazole, chloramphenicol, ampicillin, penicillin, cephalosporins) are effective. One recommended regimen is ceftriaxone (2 g IV daily) or procaine (1.2 million U IM once daily) or penicillin G (1.5-6 million U IV every 6 hours) together with streptomycin (1.0 g IM once daily for 10-14 days) and trimethoprim-sulfamethoxazole (160/800 mg orally twice daily for 1 year). In patients with sulfonamide allergy, these drugs can be replaced by oral penicillin VK or ampicillin. Clinical improvement is rapid, with fever and joint pain resolving within a few days. The intestinal symptoms of Whipple's disease usually resolve within 1 to 4 weeks.
Some authors do not recommend repeat small bowel biopsies, citing the fact that macrophages may persist for several years after treatment. However, other authors recommend repeat biopsy after 1 year of treatment. In the latter case, electron microscopy is necessary to document the presence of bacilli (not just macrophages). Relapses of the disease are possible even after years. If relapse is suspected, a small bowel biopsy (regardless of the organ or system involved) is necessary to verify the presence of free bacilli.