SUMMARY: 

Chronic diarrhea, or watery diarrhea that has lasted for more than 4 weeks, has a wide differential including infectious etiologies, inflammatory bowel disease (IBD), and functional diarrhea or irritable bowel syndrome – diarrhea predominant (IBS-D). In evaluating immunocompetent patients with chronic diarrhea and suspected IBS-D or functional diarrhea, it is important to rule out these other potentially life-threatening etiologies. To that end, the American Gastroenterological Association (AGA) has developed recommendations for the laboratory evaluation of patients with chronic diarrhea and suspected functional diarrhea or IBS-D.  

Who to Test  

• Immunocompetent patients with chronic (> 4 weeks) watery diarrhea with suspected functional diarrhea or IBS-D should undergo laboratory evaluation prior to confirming the diagnosis of IBS-D/functional diarrhea 
  • These recommendations exclude immunosuppressed patients and patients with diarrhea and “red flag” symptoms including: Bloody diarrhea | Steatorrhea | Weight loss | Anemia | Hypoalbuminemia  
  • Additionally, these recommendations exclude patients with risk factors for infectious or inflammatory diarrhea including: Family history of IBD | Family history of colon cancer | Family history of celiac disease | Travel to a region with endemic diarrheal illnesses  

Laboratory Evaluation  

• Fecal calprotectin | Fecal lactoferrin  
  • AGA suggests the use of these tests in all patients presenting with chronic diarrhea as defined above  
  • Either test may be used to screen for inflammation in the GI tract  
  • These tests are regularly used in the evaluation and follow up of patients with IBD and a negative test can help rule out IBD 
  • AGA recommends a screening cut-off value of 50 µg/g for fecal calprotectin and threshold values in the range of 4.0 to 7.25 µg/g for fecal lactoferrin to optimize sensitivity  
  • A positive result should prompt the provider to obtain further testing to evaluate for IBD  
• Giardia antigen testing | Giardia PCR 
  • Giardia is a common diarrheal causing pathogen throughout the United States 
  • Giardia antigen or PCR testing should be checked in all patients presenting with chronic diarrhea  
  • In the absence of travel from high-risk areas, routine testing for other ova and parasites is not recommended   
• Celiac serologies 
  • Celiac disease should be ruled out in all patients presenting with chronic diarrhea 
  • Screen with IgA tissue transglutaminase and IgA levels 
  • In patients with concomitant IgA deficiency, then IgG tissue transglutaminase and IgG or IgA deaminated gliadin peptides should be checked in lieu of IgA tissue transglutaminase 
  • Positive testing should prompt GI referral for EGD and biopsy 
• Bile acid diarrhea 
  • Patients with chronic diarrhea should be evaluated for bile acid diarrhea  
  • Excess production or decreased absorption of bile acids can lead to increased concentration of bile acids in the colon and resultant watery diarrhea 
  •  Tests available in the United States include: Measurement of total bile acids in a 48-hour stool collection | Serum fibroblast growth factor 19 
  • If testing is unavailable, it is reasonable to trial bile acid binders in patients with suspected bile acid diarrhea and monitor for clinical improvement to confirm diagnosis  
• ESR | CRP  
  • AGA suggests AGAINST the routine use of ESR/CRP in patients with chronic diarrhea to evaluate for possible IBD given their lack of specificity  
  • If unable to obtain fecal calprotectin or lactoferrin, then checking CRP may be considered  
  • CRP is preferred over ESR given its higher sensitivity and specificity when using a recommended cut-off of 5 to 6 mg/L 
• Serologic testing 
  • Serologic testing for IBS-D currently lacks convincing data and is not recommended by the AGA 

KEY POINTS:  

• Immunocompetent patients with chronic diarrhea in the absence of concerning “red flag” symptoms or worrisome family history should undergo laboratory evaluation to rule out other infectious and inflammatory/autoimmune etiologies of chronic diarrhea prior to making a diagnosis of functional diarrhea or IBS-D 
• Recommended testing includes Celiac serologies, Giardia testing, fecal inflammatory markers, and testing for bile acid diarrhea  

Learn More – Primary Sources:  

AGA: Laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome (IBS-D) 

ACG Clinical Guideline: Management of Irritable Bowel Syndrome 

Related PcMed Topics:

RCT Results: Does a Low-Dose Tricyclic Antidepressant Improve Irritable Bowel Syndrome?

Celiac Disease Diagnosis and Management