How is Whipples disease diagnosed
The most common means of diagnosis remains pathology and PCR, whereas culture of T. whipplei , even with the advent of specific axenic medium, can only be performed in a few laboratories. Before the PCR technique was developed, a definitive diagnosis was established only when microscopic examination of a jejunal biopsy of small intestinal mucosa showed infiltration of the lamina propria by large macrophages that contained diastase-resistant, PAS-positive inclusions. With the advent of electron microscopy in the 1960s, the rod-shaped bacteria were found in multiple other tissues (lymph nodes, pericardium, myocardium, liver, spleen, kidney, synovium, and brain) and are located both intracellularly and extracellularly. Current recommendations include an initial screen of both stool and saliva with quantitative PCR, followed by a targeted evaluation of the clinically involved organ. The sampled tissue should be sent for histology, PAS stain, quantitative PCR, and, if available, immunohistochemical staining with antisera specific for T. whipplei and electron microscopy. PCR testing of saliva and stool as a screening tool for classic Whipple’s disease has a 95% positive predictive value if both are positive and a 98% negative predictive value if both are negative. However, the sensitivity of PCR drops to 36% for saliva and 64% for stool in patients with focal T. whipplei infections. Therefore, the gold standard for a confident diagnosis is demonstration of the organism in one involved tissue (usually small bowel) by at least two methods (PAS stain, PCR, or immunohistochemical stain) or the demonstration of the organism by PCR testing in two involved sites (e.g., synovial fluid and CSF). Note that all patients regardless of presence or absence of neurologic symptoms should have a PCR of their CSF performed to rule out occult CNS infection.
