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ESSENTIALS OF DIAGNOSIS

  • Rare disease (1 in 1,000,000) caused by Tropheryma whipplei (TW).

  • Mainly presents in middle-aged/older males.

  • Large joint arthritis is the most common manifestation and precedes the development of systemic symptoms by many years.

  • The four cardinal signs are arthritis, weight loss, abdominal pain, and diarrhea.

  • Oculomasticatory myorhythmia (OMM) is a pathognomonic but late manifestation.

  • Diagnosis is made by demonstration of characteristic periodic acid–Schiff (PAS)-positive intracellular inclusions and identification of TW by polymerase chain reaction (PCR) of involved tissues or fluids.

  • All patients with confirmed Whipple disease should have PCR for TW tested on cerebrospinal fluid (CSF), even those without neurological symptoms.

  • Prolonged antibiotic treatment is required (>1 year).

General Considerations

Whipple disease, a chronic multisystem disease caused by infection with Tropheryma whipplei, was first described in 1907 by George H. Whipple who detected at autopsy the presence of rod-shaped organisms within the vacuoles of foamy macrophages in the intestine of a 36-year-old man clinician. Over 40 years later, these cells were found to stain positively with periodic acid Schiff (PAS). In 1961, electron microscopy demonstrated bacterial components in these tissues. Identification of the bacillus was reported in 1992 with the aid of polymerase chain reaction (PCR), 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 potentially fatal disease.

Whipple disease is rare, with an estimated incidence of 1 per million. It occurs most commonly 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 characterized by fatigue and joint pains, with or without synovitis. Later, abdominal pain, diarrhea, weight loss, 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 is ubiquitous and can be found in the general environment. It has also been isolated from the saliva, dental plaque, 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. IgG antibodies against T whipplei can be detected in up to 70% of healthy people. Therefore, not everybody who is exposed to infection will develop clinical symptoms. Although host factors appear to play a role in disease manifestation, no specific genetic link has been identified.

There is strikingly little inflammation in tissues infected with T whipplei. The organism does not provoke a local cytotoxic reaction and large numbers of bacilli accumulate in involved tissue. These observations have led to suggestions that aberrations of the host immune response may contribute ...

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