Chronic unexplained diarrhea: what to do when the initial workup is negative?

Diagnosing the patient with chronic diarrhea can still be a major challenge despite modern testing. It is useful initially to consider what may be the likely underlying pathophysiologic explanation for diarrhea from the history (osmotic, secretory, inflammatory, or motility related) and let this information drive the management algorithm. However, gastroenterologists frequently ask how far the workup should go and when a confident diagnosis of functional diarrhea can be made. In contrast to diarrhea-predominant irritable bowel syndrome, the evidence that functional diarrhea exists as a real diagnostic entity is actually remarkably unconvincing.