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 Physiological and Microbiological Testing?


21. Breath tests can assist with the diagnosis of carbohydrate malabsorption and SIBO. Sensitivity and specificity are variable; therefore, breath tests are not recommended without local validation. (2b)

22. Idiopathic BAM may be more frequent than previously appreciated. Until more specific tests for BAM become widely available, empiric therapy may be the only option available in many clinical settings. (2b)

23. Direct pancreatic function testing is not widely available. Indirect testing (eg, serum trypsin, fecal chymotrypsin, and fecal elastase assays) has limited sensitivity. Imaging and empiric trials of pancreatic enzyme replacement therapy may be the best available methods for assessing the role of pancreatic insufficiency in patients with steatorrhea. (2c)

Hydrogen Breath Tests. Hydrogen (H2) production in mammals is due to bacterial metabolism of carbohydrates, allowing development of technologies to detect malabsorption of carbohydrates and SIBO.[66] If carbohydrate, eg, lactose or fructose, is malabsorbed, colonic bacteria metabolize the carbohydrate and produce H2. Similarly, in SIBO, the bacteria in the small intestine degrade nutrients before they can be absorbed, again producing H2. The H2 diffuses across the gut wall into the bloodstream, is excreted by the lungs, and can be detected in the breath.

SIBO is generally associated with anatomic or functional abnormalities of the intestine such as strictures, achlorhydria, motility disorders, or scleroderma. Symptoms related to SIBO include diarrhea, bloating, and weight loss. The diagnostic gold standard, quantitative culture of intestinal aspirates, is uncommonly performed in practice. Instead, hydrogen breath tests that use glucose or lactulose are more commonly used. However, sensitivity and specificity of these tests vary widely, resulting in questionable reliability.[66]

SIBO has increasingly been implicated as a factor in IBS with diarrhea on the basis of lactulose hydrogen breath tests.[67] However, other studies have not confirmed the frequent diagnosis of SIBO in IBS patients.[68] Increased sensitivity and specificity may be gained by simultaneous measurement of intestinal transit time, which permits an accurate determination of whether the hydrogen signal arises from the small bowel or colon.[69]

Bile Acid Malabsorption. Our understanding of the pathophysiology, clinical presentation, and treatment of BAM is changing rapidly. Although classic BAM as a result of ileal resection or disease remains uncommon, there has been an increasing interest in idiopathic BAM that may be related to functional diarrhea or diarrhea-predominant IBS in as many as 33%–60% of cases.[70,71] Emerging evidence suggests that there may be a paradoxical increase in the bile acid pool related to changes in the intestinal peptide FGF19.[70,71] There are several promising diagnostic studies that unfortunately are not widely available.[72] Whole-body retention of selenium-75-homocholic acid taurine is used in Europe and Canada as a measure of BAM, but it is not available in the United States.[73] Quantitative stool bile acids and measurement of C4, an indicator of bile acid synthesis and pool size, may be performed in a limited number of academic centers.[71] Patients with an abnormal selenium-75-homocholic acid taurine test (<10% retention) predictably respond to bile acid binding drugs, whereas those with normal retention do not.[71,72,74] Better understanding of the pathophysiology of BAM may lead to innovative therapies in the near future.[75,76] If specific testing is not available, clinicians often resort to empiric trials, which not unexpectedly have a much less predictable response.[74,75,77]

Pancreatic Function Testing. Testing for pancreatic insufficiency is difficult.[50] The gold standard, the secretin stimulation test, is cumbersome and rarely performed. In a modified, endoscopic secretin stimulation test, the pancreatic duct is cannulated during endoscopic retrograde cholangiopancreatography for fluid collection, but diagnostic accuracy is a concern.[78]

Other tests of pancreatic function, including serum trypsin, fecal chymotrypsin, and fecal elastase,[50] are attractive because of their relative simplicity. However, they have limited ability to detect mild pancreatic insufficiency.

Imaging to diagnose chronic pancreatitis is based on detecting the abnormal anatomy, such as with endoscopic ultrasound and MR imaging without and with secretin.[50]

In practice, many clinicians opt for an empiric trial of pancreatic enzyme replacement when pancreatic insufficiency is considered a potential cause for diarrhea. Although there are some intricacies to evaluating the results of empiric enzyme replacement therapy, a symptomatic response and reduction in steatorrhea may be sufficient to establish a diagnosis in the appropriate clinical setting.