Gastrointestinal: Whipple's disease: Often taught but rarely seen and diagnosed late

A 62-year-old Caucasian woman presented with a 3-year history of progressive weight loss (overall 17 kg, current BMI 16 kg/m2), watery diarrhea, joint pains, sub-febril temperatures up to 38.5 degrees, and weakness. Two years ago, a rheumatologist revealed the diagnosis of seronegative polyarthritis due to pain, swelling and inflammation of multiple small and large joints. During therapy with corticosteroids and methotrexate over 3 months, fever increased with no improvement in joint problems. Thus, this treatment was canceled. Within the last year, the patient underwent extensive investigations in three other hospitals, including endoscopy of the upper and lower gastrointestinal tract with step biopsies, bone marrow biopsy, computed and positron emission tomography, in which a malignant tumor as well as coeliac and inflammatory bowel diseases could be excluded. Suspecting an unknown systemic disease, we performed again extensive microbiological and laboratory investigations. We found only mild elevations of leucocytes (12/nl) and the C-reactive protein (2.8 mg/dL; range < 0.5). Tuberculosis, HIV infection, systemic vasculitis and endocarditis were excluded. As computed tomography showed enlarged mesenteric lymph nodes, we repeated esophagogastroduodenoscopy. Duodenal biopsies revealed pathognomonic histological findings (Fig. 1) and its PCR analysis detected specific DNA of Trophyrema whipplei confirming the definitive diagnosis of Whipple's disease (WD). Consequently, we initiated antibiotic therapy with ceftriaxone intravenously for 2 weeks with rapid improvement of complaints. Thereafter, we started with oral trimethoprim-sulfamethoxazole for 1 year. WD is a chronic multi-systemic infection with the Gram-positive bacterium Trophyrema whipplei that is found ubiquitously in the environment. Middle-aged Caucasian men are predominantly affected. According to an inpatient database, the most common reason for admission of people with WD was a gastrointestinal manifestation (25.5%), circulatory/cardiovascular and musculoskeletal diseases each comprised 11.2% of primary diagnoses, whereas diseases of the central nervous system (particularly encephalopathy or meningoencephalitis) represented 6.1%. Our case reflects the typical multi-organ involvement and its diagnostic problems. Due to its patchy pattern, repeated biopsies from affected tissues—in particular from the small intestine with macro forceps—are often required. In cases with jejunal or ileal involvement, the diagnosis was rarely made through (double balloon) enteroscopy or capsule endoscopy. If you are to have any chance to diagnose this rare disease (estimated overall prevalence 3–9.8 in 1 million), keep in mind its unspecific and long-term clinical presentation. As WD can be fatal without adequate therapy, you must show perseverance in suspicious cases.