Diagnostic Workup for Chronic Loose Stool
Order first-line laboratory tests including complete blood count, C-reactive protein, IgA tissue transglutaminase with total IgA level, and stool testing for Giardia antigen, as these have the highest yield for identifying treatable causes of chronic diarrhea. 1
Initial Laboratory Panel
The following tests should be ordered immediately for all patients with chronic diarrhea:
- Complete blood count (CBC) to screen for anemia and inflammatory conditions 1, 2
- C-reactive protein (CRP) to identify inflammatory processes 1, 2
- IgA tissue transglutaminase (tTG-IgA) with total IgA level to screen for celiac disease, which has sensitivity and specificity exceeding 90% 1
- Critical pitfall: Always order total IgA alongside tTG-IgA, as IgA deficiency causes false-negative results and is commonly missed 1
- Giardia antigen test or PCR with sensitivity and specificity greater than 95% 1
- Basic metabolic panel to assess electrolyte abnormalities 2
Risk-Stratified Additional Testing
If Patient Has Specific Risk Factors:
- SeHCAT testing (preferred) or serum C4 assay for bile acid diarrhea if the patient has history of:
If Alarm Features Present:
Order colonoscopy with biopsies when any of the following are present 1:
- Blood in stool 1
- Unintentional weight loss 1
- Elevated inflammatory markers (CRP) 1
- Nocturnal diarrhea 1
- Symptoms less than 3 months duration 1
Critical requirement for colonoscopy: Obtain biopsies from both right and left colon even if mucosa appears normal, as microscopic colitis cannot be diagnosed without histology 3
Stool Studies for Categorization
If initial testing is unrevealing, order stool studies to categorize diarrhea type 2:
- Fecal calprotectin to assess for intestinal inflammation 3
- Stool osmotic gap to distinguish osmotic from secretory diarrhea 2
- Fecal fat testing if malabsorption suspected 2
Common Diagnostic Pitfalls to Avoid
- Do not skip celiac and Giardia testing regardless of symptom presentation—these must be tested in all patients 1
- Do not order broad ova and parasite panels in patients without travel history, as yield is extremely low 1
- Do not assume functional diarrhea based on Rome IV criteria alone, as these have only 52-74% specificity and do not reliably exclude IBD, microscopic colitis, or bile acid diarrhea 1, 3
- Review all medications as potential causes, particularly proton pump inhibitors, antibiotics, and metformin 1, 3
- Do not overlook bile acid diarrhea in patients with prior cholecystectomy or ileal resection 1, 3
When to Refer for Endoscopy
Upper endoscopy with duodenal biopsies is indicated when 1:
- Celiac serology is positive (to confirm diagnosis) 1
- Symptoms suggest malabsorption (bulky, pale, malodorous stools) 1
Colonoscopy with terminal ileal intubation (aim for >90% cecal intubation rate) is indicated when 1:
- Inflammatory markers elevated 1
- Alarm features present 1
- Initial testing unrevealing but symptoms persist and impair quality of life 1
Additional Considerations
- Lactose intolerance testing with hydrogen breath test if dietary history suggests lactose as trigger 1
- Small intestinal bacterial overgrowth (SIBO) should be considered, though empirical antibiotic trial is preferred over routine breath testing 1, 3
- Laxative abuse screening with stool/urine testing if suspected based on history 1
Approximately two-thirds of chronic diarrhea cases can be diagnosed with this systematic approach 3, and multidisciplinary management including gastroenterology, dietetics, and psychology may be needed for complex cases 3.