What are the diagnostic steps and treatment options for chronic diarrhea?

Chronic Diarrhea Testing: Diagnostic Algorithm

Begin with a detailed clinical history focusing on duration, stool characteristics (watery vs. bloody vs. fatty), nocturnal symptoms, weight loss, and medication review, followed by first-line blood and stool screening tests to distinguish organic from functional causes and guide further targeted investigation. 1

Initial Clinical Assessment

Red flags indicating organic disease that warrant aggressive investigation include: 1

• Diarrhea duration less than 3 months
• Nocturnal or continuous (not intermittent) diarrhea
• Significant weight loss
• Blood or mucus in stool

Key history elements to elicit: 1

• Family history of inflammatory bowel disease, celiac disease, or colorectal cancer
• Surgical history, particularly ileal resection, cholecystectomy, or gastric surgery (increases risk of bile acid malabsorption and bacterial overgrowth)
• Medication review (up to 4% of chronic diarrhea cases are drug-induced) 1
• Alcohol use (causes rapid transit, disaccharidase deficiency, pancreatic dysfunction) 1
• Systemic diseases including diabetes, thyroid disease, or immunocompromise 1

First-Line Screening Tests

Mandatory initial blood tests: 1

• Complete blood count (to exclude anemia)
• Anti-tissue transglutaminase IgA with total IgA (celiac disease screening)
• C-reactive protein or ESR
• Basic metabolic panel (electrolytes, renal function)
• Liver function tests
• Thyroid function tests
• Vitamin B12, folate, iron studies 1

Mandatory initial stool tests: 1

• Fecal calprotectin to exclude colonic inflammation (particularly in patients <40 years with IBS-like symptoms)
• Stool culture and microscopy for infections (especially in immunocompromised or elderly patients) 1

Categorization-Based Testing

After initial screening, categorize diarrhea as watery, fatty (malabsorptive), or inflammatory to guide further testing: 1, 2

For Watery Diarrhea (Functional/Secretory/Osmotic)

If IBS criteria are met after negative screening tests, make a positive IBS diagnosis without further testing. 1

If functional bowel disorder or IBS-diarrhea is suspected, test for bile acid diarrhea: 1

• SeHCAT testing (preferred) or serum 7α-hydroxy-4-cholesten-3-one
• Do NOT use empirical cholestyramine trial instead of making a positive diagnosis 1

For suspected lactose intolerance: 1

• Hydrogen breath testing (if available) or
• Empirical dietary lactose withdrawal

For suspected small bowel bacterial overgrowth: 1

• Empirical antibiotic trial is recommended rather than routine breath testing

For Fatty Diarrhea (Malabsorption)

If celiac disease serology is positive, proceed to upper endoscopy with duodenal biopsies. 1

For suspected pancreatic insufficiency: 1

• Fecal elastase testing (do NOT use PABA testing)
• MRI (not CT) for structural pancreatic abnormalities

For small bowel evaluation: 1

• MR enterography (first-line for small bowel abnormalities)
• Video capsule endoscopy (alternative based on local availability)
• Do NOT use small bowel barium follow-through (poor sensitivity/specificity)
• Reserve enteroscopy only for targeted lesions identified by MR enterography or capsule endoscopy

For Inflammatory Diarrhea

For patients with altered bowel habit ± rectal bleeding: 1

• Colonoscopy to exclude colorectal cancer (mandatory in appropriate age groups)
• Fecal immunochemical testing can guide priority of investigations in those without rectal bleeding

For suspected microscopic colitis: 1

• Colonoscopy with biopsies from right and left colon (NOT rectal biopsies)

For suspected infectious causes: 1

• Stool testing for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and STEC
• Test for Yersinia in patients with persistent right lower quadrant pain
• Test for Vibrio in patients with rice-water stools or shellfish exposure
• Blood cultures in infants <3 months, signs of sepsis, or suspected enteric fever

When Shiga toxin-producing organisms are suspected: 1

• Use diagnostic approaches detecting Shiga toxin or genes encoding them
• Distinguish E. coli O157:H7 from other STEC

Secondary Assessment for Persistent Symptoms

If symptoms persist despite normal first-line investigations and treatment, refer for: 1

• Repeat blood and stool tests to exclude malabsorption
• Infectious workup (especially in immunocompromised or elderly)
• Consider factitious diarrhea in patients with psychiatric history or eating disorders 1

Common Pitfalls to Avoid

• Do not diagnose IBS without basic screening tests (celiac serology, inflammatory markers) 1
• Do not overlook medication-induced diarrhea—review all medications systematically 1, 3
• Do not use empirical bile acid sequestrant therapy without confirming bile acid diarrhea diagnosis 1
• Do not perform colonoscopy for microscopic colitis without taking biopsies from right and left colon (rectal biopsies are inadequate) 1
• Do not order barium studies for small bowel evaluation (obsolete due to poor diagnostic yield) 1
• Evaluate for dehydration in all patients, particularly young children and elderly, as this increases mortality risk 1