Approach Considerations

Biopsy of the appropriate tissue is essential for establishing a diagnosis. These tissues may include small bowel, brain, endocardial, and synovial. Biopsies of tissue samples from the small bowel show expanded villi containing macrophages staining positive with periodic acid-Schiff stain. This finding leads to electron microscopy and then DNA testing for T whipplei.

A baseline lumbar puncture to obtain cerebrospinal fluid (CSF) analysis for T whipplei should be obtained in newly diagnosed patients, even if the patient has a normal neurologic examination.

Laboratory Studies

Basic laboratory studies that suggest the presence of malabsorption may be useful screening tests, as follows:

Sudan stain of stool
Serum carotene
Serum albumin
Prothrombin time

The definitive test for the presence of malabsorption is the 72-hour fecal fat determination.

Abnormalities in any of these laboratory test results suggest that malabsorption is present, but they are not specific for Whipple disease.

Imaging Studies

Imaging studies, such as computed tomography (CT) scanning and a small-bowel series, may suggest the presence of malabsorption, but these imaging studies are not specific for Whipple disease.

Brain magnetic resonance imaging (MRI) may demonstrate T1, T2, and fluid-attenuated inversion recovery abnormalities in the cerebellar peduncles, vermis, medulla, and foci of enhancement in the subcortical white matter, but these abnormalities are not pathognomonic for Whipple disease.

Other Tests

No tests are specific for diagnosis except determining the presence of T whipplei DNA through PCR.^[37]However, this test is not available universally. Polymerase chain reaction (PCR) currently is performed only at a few centers, including the Mayo Clinic and Stanford University.

Availability and cost are prohibitive to obtaining this test. Check for availability with the medical laboratory and for cost approval with each hospital or office laboratory used by the practice.

Immunoglobulin G (IgG) antibody for T whipplei should not be used diagnostically, as up to 70% of control subjects demonstrate the antibody. IgM antibody is more specific but not easily available.

A real-time PCR assay that targets a segment of the rpoB gene specific to T whippeli has been reported to be highly sensitive for the detection of T whipplei.^[38]

Histologic Findings

For intestinal disease, a small-bowel biopsy may show the lamina propria of the small bowel full of periodic acid-Schiff–positive macrophages. Endocardial, brain, or synovial biopsies may show similar changes for Whipple endocarditis, CNS Whipple disease, or synovial Whipple disease, respectively.^[39]The presence of T whipplei by PCR in patients who are clinically symptomatic is pathognomonic for the disease.

Treatment & Management

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