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 long-term antibiotics.
In the United States, Whipple disease is rare, affecting White individuals over age 30 and more commonly over age 60; in some parts of the world, however, it is endemic (1, 2). Some, but not all, studies report a male predominance. 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 (3, 4).
References
1. Porteiro B, Freitas AR, Nunes F, Major M, Batista F. Whipple's Disease: A Challenging Diagnosis. Cureus. 2024;16(1):e51991. Published 2024 Jan 10. doi:10.7759/cureus.51991
2. Lagier JC, Raoult D. Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them. Curr Opin Infect Dis. 2018;31(6):463-470. doi:10.1097/QCO.0000000000000489
3. Elchert JA, Mansoor E, Abou-Saleh M, Cooper GS. Epidemiology of Whipple's Disease in the USA Between 2012 and 2017: A Population-Based National Study. Dig Dis Sci. 2019;64(5):1305-1311. doi:10.1007/s10620-018-5393-9
4. Ahmad AI, Wikholm C, Pothoulakis I, et al. Whipple's disease review, prevalence, mortality, and characteristics in the United States: A cross-sectional national inpatient study. Medicine (Baltimore). 2022;101(49):e32231. doi:10.1097/MD.0000000000032231
Symptoms and Signs of Whipple Disease
Clinical presentation varies depending on the organ systems affected. The 4 cardinal symptoms of Whipple disease are
Arthralgia
Diarrhea
Abdominal pain
Weight loss
Usually, the first symptoms are arthralgia 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, endocarditis, and central nervous system symptoms.
Diagnosis of Whipple Disease
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 or older White individuals with 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 testing and immunohistochemistry should be performed.
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 of Whipple Disease
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 intravenous ceftriaxone or penicillin G for 2 to 4 weeks. This regimen is followed by a long-term course of oral therapy with trimethoprim/sulfamethoxazole or a combination of doxycycline and hydroxychloroquine. 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., cephalosporins). Treatment of Whipple disease is initiated with intravenous ceftriaxone or penicillin G for 2 to 4 weeks. This regimen is followed by a long-term course of oral therapy with trimethoprim/sulfamethoxazole or a combination of doxycycline and hydroxychloroquine. 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, polymerase chain reaction (PCR) testing can be performed on stool, saliva, or other tissue. However, other authorities recommend periodic follow-up biopsies with microscopy and PCR testing (1).
Relapses are common and may occur years later. If relapse is suspected, small-bowel biopsies and/or PCR testing should be performed (regardless of affected organ systems) to determine presence of free bacilli.
Treatment reference
1. Lagier JC, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult D. Treatment of classic Whipple's disease: from in vitro results to clinical outcome. J Antimicrob Chemother. 2014;69(1):219-227. doi:10.1093/jac/dkt310
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 or older White individuals 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.
