Making the diagnosis

Whenever the suspicion arises that a patient may suffer from Whipple´s disease, the best way to check this possibility is a histologic study of small intestinal biopsies. For this purpose, at least five mucosal biopsy particles should be obtained from the most distal part of the duodenum which can be reached with the endoscope:
- when intestinal histology is reported as normal, Whipple´s disease can bona fide be ruled out. There are only very few exceptions to this rule.
- in the case that intestinal histology is characteristic, or at least suspicious of Whipple´s disease additional studies should be performed until confirmation is reached (PCR, electron microscopy).

To find more information about the histopathology of intestinal Whipple´s disease, click to the buttom.

For information about PCR analysis of intestinal biopsies, click the buttom.

Initial staging

Once the diagnosis of Whipple´s disease is established, further diagnostic studies should be perfomed before treatment is started. These studies intend to look for the possible extent of infection spreading from the small intestine.


Even in patients without neurologic or psychiatric symptoms, diagnostic staging also includes lumbar puncture to obatin a sample of cerebrospinal fluid (CSF). For cytologic analysis, a fresh CSF sample should be processed for cytologic preparation within 30 to 60 minutes. For PCR analysis, a further 2 ml sample should be frozen, and sent to a suitable lab on dry ice.

For more information about cytology and  PCR analysis of CerebroSpinal Fluid samples, click the buttom.

Monitoring during therapy

After start of antibiotic treatment, intestinal symptoms usually ameliorate within a week. Beside remission of symptoms, the regression of abnormal clinical, diagnostic imaging, and laboratory findings should be monitored at intervals. Endoscopic lesions usually resolve within three to eight months, while histology is still abnormal. Abdominal lymphadenopathy may last for more than a year. 

Prior to stop of treatment, analysis of the CSF should be repeated to document whether eradication of cerebral  infection is reached.

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