What is the approach to diagnosing and evaluating chronic diarrhea?

Diagnostic Approach to Chronic Diarrhea

Begin with a structured algorithmic approach starting with first-line investigations in primary care, followed by colonoscopy for those over 45 or with alarm features, and targeted testing based on stool characteristics and clinical patterns. 1

Definition and Initial Triage

Chronic diarrhea is defined as ≥3 loose or liquid stools per day for more than 4 weeks. 2 This 4-week cutoff distinguishes infectious from non-infectious etiologies and triggers systematic investigation. 2

Immediately assess for alarm features that mandate urgent evaluation: 3, 4

• Nocturnal diarrhea (suggests organic disease)
• Unintentional weight loss (excludes IBS, raises concern for malignancy/IBD)
• Blood in stool or positive fecal occult blood
• Fever
• Recent onset (<3 months duration)
• Age >45-50 years

First-Line Investigations (Primary Care Setting)

All patients require baseline blood and stool testing before proceeding to endoscopy: 1, 3

Blood Tests

• Complete blood count, C-reactive protein
• Electrolytes, liver function tests
• Iron studies, vitamin B12, folate
• Thyroid function tests (TSH)
• Anti-tissue transglutaminase IgA with total IgA (celiac screening—do not skip this) 3, 5

Stool Studies

• Fecal calprotectin to exclude colonic inflammation (strong recommendation for those <40 with suspected IBS) 1
• Fecal immunochemical testing (FIT) for occult blood 1
• Stool culture and ova/parasites if infectious etiology suspected 4

Endoscopic Evaluation Strategy

Age-Stratified Colonoscopy Approach

For patients ≥45 years or any age with alarm features: Full colonoscopy with biopsies is mandatory. 1, 3, 4 The diagnostic yield ranges from 7-31% and is essential to exclude colorectal cancer (27% prevalence in those with altered bowel habit) and inflammatory bowel disease. 4

For patients <40-45 years without alarm features and normal fecal calprotectin: Flexible sigmoidoscopy may be sufficient initially. 1, 3 However, note that approximately 50% of neoplasia occurs proximal to the splenic flexure, so maintain a low threshold for full colonoscopy. 4

Critical Biopsy Protocol

Obtain biopsies from right and left colon (not rectum) even if mucosa appears normal to exclude microscopic colitis, which accounts for 15% of chronic diarrhea cases in older adults and can only be diagnosed histologically. 1, 4

Secondary Assessment for Persistent Symptoms

If initial investigations are normal and symptoms persist, proceed with targeted testing based on clinical phenotype: 1

For Suspected Malabsorption (bulky, pale, malodorous stools)

Small bowel evaluation:

• MR enterography (preferred) or video capsule endoscopy for small bowel abnormalities 1
• Do NOT use small bowel barium studies—poor sensitivity and specificity 1
• Upper endoscopy with distal duodenal biopsies if celiac serology negative but suspicion remains 1

Pancreatic evaluation:

• Fecal elastase testing when fat malabsorption suspected (do NOT use PABA testing) 1
• MRI (not CT) for structural pancreatic abnormalities in suspected chronic pancreatitis 1

For Functional Bowel/IBS-Diarrhea Pattern

Make a positive diagnosis of bile acid diarrhea using SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one (depending on local availability). 1 Do NOT use empirical trials of bile acid sequestrants without diagnostic confirmation—insufficient evidence supports this approach. 1

For Suspected Small Intestinal Bacterial Overgrowth (SIBO)

Use an empirical trial of antibiotics rather than breath testing, as hydrogen/methane breath tests have only ~60% sensitivity and ~75% specificity. 1

For Carbohydrate Malabsorption

If lactose maldigestion suspected, use hydrogen breath testing if available, or trial dietary lactose/carbohydrate withdrawal. 1

Common Pitfalls to Avoid

• Never diagnose IBS in the presence of weight loss—this is an exclusion criterion for functional disorders. 4
• Do not skip colonic biopsies even with normal-appearing mucosa—microscopic colitis requires histologic diagnosis. 4
• Do not perform flexible sigmoidoscopy alone in patients with alarm features—full colonoscopy is required. 4
• Do not use empirical bile acid sequestrant therapy without diagnostic confirmation. 1
• Avoid small bowel barium studies—they have been supplanted by MR enterography and capsule endoscopy. 1

Rare Causes (Test Only After Excluding Common Etiologies)

Hormone-secreting tumors are rare causes of diarrhea and should only be investigated after excluding all common causes. 1 Similarly, anorectal manometry and endoanal ultrasound should only be used when other local pathology has been excluded and conservative measures exhausted. 1

When Diagnosis Remains Elusive

Approximately two-thirds of cases can be diagnosed using this algorithmic approach. 1 For the remaining patients with persistent symptoms despite exhaustive evaluation, the prognosis is generally good, and symptomatic treatment with antidiarrheal agents (loperamide, cholestyramine, bulking agents) is appropriate. 1, 6