Approach to the diagnosis of Whipple's disease

CNS: central nervous system; CSF: cerebrospinal fluid; HIV: human immunodeficiency virus; PAS: periodic acid-Schiff; PCR: polymerase chain reaction.
* Classic Whipple's disease is a multisystemic process that presents over time. Joint symptoms, typically migratory arthralgias of the large joints, generally precede other manifestations by many years. Later in the course of disease, intermittent diarrhea with colicky abdominal pain occur and ultimately progress to a severe wasting syndrome. Many other organ systems can also be affected, including the central nervous system.
¶ The first step in the evaluation of Whipple's disease is to assess for alternative, more common disorders that cause chronic diarrhea, arthralgias, or progressive CNS disease. The differential diagnosis is wide and depends on the presentation.
Δ Endoscopy with small bowel biopsy is a safe and simple diagnostic test that we perform whenever the possibility of Whipple's disease is being considered, even in patients with predominantly extraintestinal features. We typically obtain seven to ten biopsies from different parts of the duodenum and, if possible, sample the stomach and proximal jejunum.
◊ CSF PCR, if not already performed, is checked on all patients diagnosed with Whipple's disease to evaluate for CNS involvement.