What is the initial evaluation and management for a patient presenting with chronic diarrhea?

Evaluation for Chronic Diarrhea

Begin the evaluation of chronic diarrhea with a detailed history focusing on alarm features (blood in stool, unintentional weight loss, nocturnal symptoms, duration <3 months), followed by first-line laboratory testing including complete blood count, C-reactive protein, IgA tissue transglutaminase with total IgA level, and stool testing for Giardia. 1

Initial History and Risk Assessment

Key historical elements to elicit:

• Duration and pattern: Symptoms <3 months duration or nocturnal diarrhea suggest organic disease rather than functional disorders 1
• Stool characteristics: Distinguish watery, bloody/mucoid, or greasy stools to guide differential diagnosis 1, 2
• Alarm features: Blood in stool, unintentional weight loss, fever, or recent change in bowel habit warrant urgent evaluation 1
• Surgical history: Terminal ileal resection, cholecystectomy, or abdominal radiotherapy are strong risk factors for bile acid diarrhea 1
• Medication review: Antibiotics, antacids, proton pump inhibitors, metformin, and other medications are common culprits 1, 3
• Travel history: Recent travel to or immigration from high-risk areas changes the testing approach 1

First-Line Laboratory Testing

Mandatory initial tests for all patients:

• Celiac disease screening: IgA tissue transglutaminase (IgA-tTG) plus total IgA level to detect IgA deficiency 1, 3

  • If IgA deficient, use IgG tissue transglutaminase or IgG deaminated gliadin peptides 1
  • Sensitivity and specificity of IgA-tTG exceed 90% when using thresholds of 7-15 AU/mL 1

• Giardia testing: Use Giardia antigen test or PCR, which have sensitivity and specificity >95% 1

  • This is a strong recommendation even without travel history, as Giardia is common throughout the United States 1

• Complete blood count and C-reactive protein: To screen for inflammatory conditions and anemia 1, 2

• Basic metabolic panel: To assess electrolyte disturbances and renal function 2

Avoid routine ova and parasite testing (other than Giardia) in patients without travel to or recent immigration from high-risk areas, as the yield is extremely low 1

Categorization by Stool Studies

When the differential diagnosis remains broad after initial testing, categorize diarrhea type using stool studies:

• Fecal calprotectin or lactoferrin: Elevated levels suggest inflammatory diarrhea (IBD, microscopic colitis, infection) 1
• Stool fat or elastase: Assess for malabsorption or pancreatic insufficiency 1, 2
• Stool osmotic gap: Helps distinguish osmotic from secretory diarrhea 2

The three main categories are watery (secretory, osmotic, or functional), fatty (malabsorption), and inflammatory diarrhea 3, 2

Bile Acid Diarrhea Assessment

For patients with specific risk factors (terminal ileal resection, cholecystectomy, or radiotherapy), strongly consider bile acid diarrhea:

• SeHCAT testing (if available) is the preferred diagnostic test 1
• Serum C4 assay can be used as an alternative where SeHCAT is unavailable 1
• Empiric trial of bile acid sequestrants may be considered when testing is unavailable, though formal diagnosis is preferred 1

Do not rely on symptom presentation alone to identify bile acid diarrhea, as no symptoms consistently predict positive testing 1

Endoscopic Evaluation

Colonoscopy with biopsies is indicated when:

• Inflammatory markers are elevated (elevated CRP or fecal calprotectin) 1
• Alarm features are present 1
• Initial testing is unrevealing but symptoms persist and impair quality of life 1
• Microscopic colitis is suspected (obtain biopsies even with normal-appearing mucosa) 1

Upper endoscopy with duodenal biopsies should be performed when celiac serology is positive to confirm the diagnosis 1

Common Pitfalls to Avoid

• Failing to test for celiac disease and Giardia in all patients with chronic diarrhea, regardless of symptom presentation 1
• Ordering broad ova and parasite panels in patients without travel history, which has extremely low yield 1
• Neglecting medication review as a potential cause, particularly proton pump inhibitors, antibiotics, and metformin 1, 3
• Missing IgA deficiency when interpreting celiac serology, which causes false-negative IgA-tTG results 1
• Assuming functional diarrhea based on Rome IV criteria alone, as these criteria have only 52-74% specificity and do not reliably exclude IBD, microscopic colitis, or bile acid diarrhea 1
• Overlooking bile acid diarrhea in patients with prior cholecystectomy or ileal resection 1

Algorithmic Approach Summary

1. Obtain detailed history focusing on alarm features, surgical history, medications, and travel
2. Perform first-line testing: CBC, CRP, IgA-tTG with total IgA, Giardia testing, basic metabolic panel
3. If alarm features present or inflammatory markers elevated: Proceed directly to colonoscopy with biopsies
4. If specific risk factors for bile acid diarrhea: Consider SeHCAT or C4 testing, or empiric bile acid sequestrant trial
5. If initial testing unrevealing: Categorize by stool studies (inflammatory vs. fatty vs. watery) to guide further evaluation
6. Consider endoscopy if symptoms persist, impair quality of life, or initial testing suggests organic disease