- Weight loss, diarrhea, and abdominal discomfort are present in 85–90% of patients at time of diagnosis.
- An intermittent, migratory oligoarthritis occurs early in the disease course, preceding gastrointestinal symptoms by an average of 6–8 years.
- Inflammatory polyarthritis and sacroiliitis can develop in the chronic phase of disease.
- Neurologic involvement is present in 90% of cases.
- Diagnosis is based on demonstration of characteristic periodic acid–Schiff (PAS)–positive intracellular inclusions and identification of Tropheryma whipplei by polymerase chain reaction (PCR) in biopsies of involved tissues or in fluids.
Whipple disease, a chronic multisystem disease caused by infection with T whipplei, was first described in 1907 by George H. Whipple who noted the presence of rod-shaped organisms in the vacuoles of foamy macrophages in the intestinal tissue of a 36-year-old man during autopsy. Over 40 years later, these cells were found to stain positively with PAS and, in 1961, electron microscopy facilitated the recognition of bacterial components in these tissues. Identification of the bacillus was reported in 1992 with the aid of the PCR technique, which enabled the amplification of specific gene segments. In 2000, the organism T whipplei was successfully cultivated in vitro, thereby facilitating developments in the pathogenesis, diagnosis, and treatment of this disease.
Whipple disease is rare, with an estimated incidence of 1 per million. It has been most commonly reported in middle-aged white men with an occupational exposure to soil, animals, or sewage. There are two recognized phases of Whipple disease. In the initial stage, symptoms and signs are nonspecific and are marked predominantly by fatigue and joint pains, with or without synovitis. In the later phase, weight loss, diarrhea, and neurologic or psychiatric symptoms may prevail. Although the average interval between these stages is 6–8 years, the initiation of immunosuppressive treatment for presumed inflammatory arthritis may unmask the diagnosis by allowing proliferation of the organism, resulting in more acute symptoms.
T whipplei can be found in the general environment, in sewage plant effluent, and in the stool in asymptomatic human carriers. It has also been isolated from the saliva, blood, stool and duodenal samples from healthy individuals, although it is unclear if this represents environmental contamination, preclinical infection, or the inconsequential presence of commensal organisms. No link with specific genetic factors has been identified.
There is a striking absence of inflammation in tissues infected with T whipplei. The organism does not provoke a local cytotoxic reaction, and large numbers of bacilli accumulate at areas of infection. These observations suggest that aberrations of the host immune response may contribute to the clinical manifestations of disease.
The diagnosis of Whipple disease requires evidence of infection with T whipplei. The test of choice usually is upper gastrointestinal endoscopy and the acquisition of multiple biopsies from the duodenum and jejunum. The tissue should be stained with PAS, which yields a 78% positivity rate for detection of characteristic intracellular inclusions in patients with untreated Whipple ...