Chronic Diarrhea: Diagnosis and Management

Lawrence R. Schiller; Darrell S. Pardi; Joseph H. Sellin


Clin Gastroenterol Hepatol. 2017;15(2):182-193. 

In This Article

What Is the Role of Endoscopy, Enteroscopy, Colonoscopy, and Mucosal Biopsy?


19. Lower gastrointestinal endoscopy with mucosal biopsy is valuable in inflammatory and secretory diarrheas. Colonoscopy has a greater yield than sigmoidoscopy, but multiple biopsies must be obtained. Biopsy of normal-appearing terminal ileum is not recommended. (1a)

20. Upper endoscopy or enteroscopy with biopsies of the duodenum or jejunum should be done in patients with unexplained steatorrhea. The role of aspiration of enteric contents for quantitative bacterial culture is unclear. (2c)

Although endoscopy and colonoscopy are not needed in every case, these tests often are useful in the evaluation of chronic diarrhea.

Lower Gastrointestinal Endoscopy. Colonoscopy with biopsy is valuable for diagnosing microscopic colitis, IBD, neoplasia, and other inflammatory conditions. Several studies have examined the diagnostic yield of colonoscopy in the evaluation of chronic diarrhea, with specific diagnoses found in 15%–31% of patients;[57,58] microscopic colitis and IBD were common.

Whether sigmoidoscopy rather than colonoscopy should suffice is unsettled. The decision revolves around whether there is a significant increase in diagnostic yield beyond 60 cm; the data are conflicting, with some studies finding a minimal increase with colonoscopy,[57] and other studies report a 10% chance of finding a specific diagnosis with inspection of the more proximal colon and ileum.[59] Therefore, colonoscopy with biopsies from the right and left colon rather than sigmoidoscopy generally is recommended.

There are few data on how many biopsies are sufficient for diagnosis of microscopic colitis; ≥8 biopsies are reasonable. There may be differences in collagen thickness and the extent of intraepithelial lymphocytosis in the rectum compared with the remainder of the colon; therefore, it is reasonable to obtain biopsies from above the rectum.[60] Although it is worthwhile to biopsy normal-appearing colon, biopsies from a normal terminal ileum are not often useful.[61]

Upper Gastrointestinal Endoscopy. There is relatively little information regarding the role of upper endoscopy in chronic diarrhea. Esophagogastroduodenoscopy (EGD) and duodenal biopsy can confirm a diagnosis of CD. However, these studies usually involve preselected individuals with positive celiac serologies and therefore do not address the diagnostic value of EGD in unselected patients with chronic diarrhea. In a large study evaluating the diagnostic value of duodenal biopsies, there was a significant finding in 8.6% of patients with diarrhea,[62] all related to the spectrum of CD. For patients with suspected or confirmed sprue, the yield of small bowel biopsies was even higher, with intraepithelial lymphocytosis in 8.9%, variable villous atrophy in 11.2%, and overt sprue in 12%.[62]

Endoscopic signs such as scalloping and furrowing have been linked to CD but are neither sensitive nor specific.[62] Endoscopic clues may suggest other diagnoses (eg, aphthous ulcers in Crohn's disease or white punctate lesions in lymphangiectasia). Nevertheless, even a normal-appearing small bowel should be biopsied in a patient with chronic diarrhea.

The effectiveness of EGD in diagnosing CD may depend on the biopsy protocol. Villous atrophy in CD may occur in the duodenal bulb alone, and so biopsies should be obtained from the bulb and the distal duodenum.[63] Despite guidelines recommending >4 biopsies for the diagnosis of CD, this occurred infrequently in 1 study.[64] It may be reasonable to take 1 biopsy per pass to preserve architectural integrity.

Communication with the pathologist can ensure that appropriate histologic techniques are used when considering rare diagnoses (eg, Congo red staining for amyloidosis, polymerase chain reaction for Tropheryma whippeli for Whipple's disease, or immunohistochemical staining for lymphoma). Upper GI endoscopy may provide additional diagnostic methodologies beyond visualization and biopsy, including duodenal aspiration for Giardia or quantitative culture. The role of capsule endoscopy and deep enteroscopy remains to be delineated.[65]