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Whipple Disease

(Whipple's Disease; Intestinal Lipodystrophy)

By

Atenodoro R. Ruiz, Jr.

, MD, The Medical City, Pasig City, Metro-Manila, Philippines

Last full review/revision Oct 2019| Content last modified Oct 2019
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Whipple disease is a rare systemic illness caused by the bacterium Tropheryma whipplei. Main symptoms are arthritis, weight loss, abdominal pain, and diarrhea. Diagnosis is by small-bowel biopsy. Treatment is initially with ceftriaxone or penicillin followed by a minimum 1 year of trimethoprim/sulfamethoxazole.

Whipple disease predominately affects white men aged 30 to 60. Although it affects many parts of the body (eg, heart, lung, brain, serous cavities, joints, eye, gastrointestinal tract), the mucosa of the small bowel is almost always involved. Affected patients may have subtle defects of cell-mediated immunity that predispose to infection with T. whipplei. About 30% of patients have the HLA-B27 gene.

Symptoms and Signs

Clinical presentation varies depending on the organ systems affected. The four cardinal symptoms of Whipple disease are

  • Arthralgia

  • Diarrhea

  • Abdominal pain

  • Weight loss

Usually, the first symptoms are arthritis and fever. Intestinal symptoms (eg, watery diarrhea, steatorrhea, abdominal pain, anorexia, weight loss) usually manifest later, sometimes years after the initial complaint. Gross or occult intestinal bleeding may occur. Severe malabsorption may be present in patients diagnosed late in the clinical course. Other findings include increased skin pigmentation, anemia, lymphadenopathy, chronic cough, serositis, peripheral edema, and central nervous system symptoms.

Diagnosis

  • Endoscopy with small-bowel biopsy

The diagnosis of Whipple disease may be missed in patients without prominent gastrointestinal symptoms. Whipple disease should be suspected in middle-aged white men who have arthritis and abdominal pain, diarrhea, weight loss, or other symptoms of malabsorption. Such patients should have upper endoscopy with small-bowel biopsy; the intestinal lesions are specific and diagnostic. The most severe and consistent changes are in the proximal small bowel. Light microscopy shows periodic acid-Schiff–positive macrophages that distort the villus architecture. Gram-positive, acid fast–negative bacilli (T. whipplei) are seen in the lamina propria and in the macrophages. If T. whipplei are not seen but Whipple disease is still clinically suspected, polymerase chain reaction (PCR) testing and immunohistochemistry should be done.

Whipple disease should be differentiated from intestinal infection with Mycobacterium avium-intracellulare (MAI), which has similar histologic findings. However, MAI stains positive with acid fast.

Treatment

  • Antibiotics

  • Late relapse a possibility

Untreated disease is progressive and fatal. Many antibiotics are curative (eg, trimethoprim/sulfamethoxazole, penicillin, cephalosporins). Treatment of Whipple disease is initiated with ceftriaxone (2 g IV daily) or penicillin G (1.5 to 6 million units IV every 6 hours) for 2 to 4 weeks. This regimen is followed by a long-term course of oral therapy with trimethoprim/sulfamethoxazole (160/800 mg 2 times a day for 1 year) or a combination of doxycycline (100 mg 2 times a day for 1 year) and hydroxychloroquine (200 mg 3 times a day for 1 year). Sulfa-allergic patients may substitute oral penicillin VK or ampicillin. Prompt clinical improvement occurs, with fever and joint pains resolving in a few days. Intestinal symptoms usually abate within 1 to 4 weeks.

To confirm response to treatment, PCR testing can be done on stool, saliva, or other tissue. However, other authorities recommend repeat biopsy after 1 year with microscopy to document bacilli (not just macrophages, which may persist for years after successful treatment) in conjunction with PCR testing.

Relapses are common and may occur years later. If relapse is suspected, small-bowel biopsies or PCR testing should be done (regardless of affected organ systems) to determine presence of free bacilli.

Key Points

  • Infection by the bacteria T. whipplei affects many organs, including the gastrointestinal tract.

  • Small bowel mucosal involvement causes malabsorption.

  • Suspect Whipple disease in middle-aged white men who have arthritis and abdominal pain, diarrhea, weight loss, or other symptoms of malabsorption.

  • Endoscopic small-bowel biopsy is necessary.

  • Long-term antibiotic treatment is necessary, and relapses are common.

Drugs Mentioned In This Article

Drug Name Select Trade
PLAQUENIL
No US brand name
ROCEPHIN
PERIOSTAT, VIBRAMYCIN
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