Because Whipple’s disease is rare, the doctor may first try to rule out more common conditions with similar symptoms, including
Whipple’s disease is diagnosed through a careful evaluation of symptoms, endoscopy, and biopsy with tissue staining. Electron microscopy and polymerase chain reaction (PCR) testing are used to confirm a diagnosis.
Endoscopy will be used to examine the lining of the small intestine. An endoscope—a thin, flexible, lighted tube with a small camera on the tip—is inserted through the mouth and stomach and into the small intestine. The endoscope transmits images taken inside the small intestine to a video monitor where a health care professional can view them.
A biopsy is performed during endoscopy to collect samples of tissue from the lining of the small intestine for examination using periodic acid-Schiff (PAS) staining. PAS is a magenta-colored stain that can reveal T. whipplei-infected cells from thinly cut tissues when viewed with a light microscope. Because PAS staining is nonspecific, meaning it can also stain cells infected with other types of bacteria and fungi, many doctors choose to confirm results with a second diagnostic test, such as electron microscopy or PCR testing.
Electron microscopy, which has a much greater resolution than light microscopy, can be used to see T. whipplei bacteria inside infected cells in the tissue taken through biopsy. T. whipplei have a unique appearance easily identified by experienced laboratories.
PCR testing can detect and identify extremely low levels of bacterial DNA in tissues and body fluids. The presence of T. whipplei DNA in cerebrospinal fluid is an indication of neurologic Whipple’s disease. PCR testing for Whipple’s disease is relatively new; therefore, results should be supported by PAS staining or electron microscopy.