What are the management options for a patient with chronic diarrhea, possibly with a history of Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD)?

Managing Chronic Diarrhea

Begin by identifying risk factors for bile acid diarrhea (BAD)—history of cholecystectomy, terminal ileal resection, or abdominal radiotherapy—as these patients have extremely high rates (68-100%) of BAD and should be considered for empiric bile acid sequestrant therapy or diagnostic testing. 1

Initial Diagnostic Approach

Screen for Inflammatory Bowel Disease

• Use fecal calprotectin (threshold ≥50 mg/g) or fecal lactoferrin (threshold 4.0-7.25 mg/g) to screen for IBD, as both have pooled sensitivity of 81% and specificity of 87% 1
• Do not rely on ESR or CRP for IBD screening, as these have inferior diagnostic accuracy (sensitivity 73%, specificity 78%) 1

Essential Laboratory Testing

• IgA tissue transglutaminase (tTG) with total IgA to detect celiac disease, which has >90% sensitivity and specificity 1
• Giardia antigen testing or PCR due to high prevalence and excellent test performance 1
• Complete blood count, comprehensive metabolic panel, and thyroid function tests to assess for anemia, malabsorption, and metabolic causes 2

Identify Bile Acid Diarrhea

Risk factors strongly predict BAD: 1

• Terminal ileal resection or right hemicolectomy for Crohn's disease: 91-100% have positive SeHCAT
• Terminal ileal resection for other reasons: 71-82% positive
• Cholecystectomy: 68-86% positive
• Radiotherapy with resection: 71-88% positive

Diagnostic testing options: 1

• SeHCAT testing (if available) with threshold <15% retention to identify BAD in IBS-D, functional diarrhea, or quiescent Crohn's disease
• Serum C4 assay as alternative when SeHCAT unavailable
• In North America where SeHCAT is unavailable, empiric trial of bile acid sequestrants is reasonable given poor tolerance and high dropout rates make diagnostic certainty valuable but not essential 1

Management Based on Etiology

Bile Acid Diarrhea Treatment

Cholestyramine is the preferred initial bile acid sequestrant over other agents (colesevelam, colestipol) for inducing clinical response 1

Dosing strategy: 1

• Start with gradual daily dose titration to minimize side effects (bloating, constipation, drug interactions)
• Alternative bile acid sequestrants should be used if cholestyramine is not tolerated

Important caveat: Avoid bile acid sequestrants in patients with Crohn's disease with extensive ileal involvement or resection, as these patients may have steatorrhea from fat malabsorption rather than BAD 1

IBS-D Management (When Functional Disorder Suspected)

First-line pharmacological therapy: 3, 4

• Loperamide 4-12 mg daily effectively reduces stool frequency, urgency, and fecal soiling
• Soluble fiber (ispaghula/psyllium) 3-4 g/day, gradually increased to avoid bloating

Second-line therapy for refractory symptoms: 3, 4

• Tricyclic antidepressants (amitriptyline 10 mg at bedtime, titrate to 30-50 mg) are the most effective pharmacological treatment for global IBS symptoms and abdominal pain
• 5-HT3 receptor antagonists (ondansetron) are likely the most efficacious drug class for IBS-D refractory to loperamide
• Rifaximin 550 mg three times daily for 14 days is FDA-approved for IBS-D, with 41% achieving adequate relief versus 31-32% with placebo 5

Dietary interventions: 3

• Low FODMAP diet as second-line therapy, supervised by trained dietitian with planned reintroduction
• Regular exercise improves overall IBS symptoms

When to Consider Colonoscopy

Colonoscopy with biopsies is mandatory when: 1, 2

• Red flag symptoms present: bloody diarrhea, weight loss, anemia, nocturnal diarrhea, palpable abdominal mass
• Age-appropriate colorectal cancer screening not completed
• Fecal calprotectin or lactoferrin elevated
• Need to exclude microscopic colitis (requires right and left colon biopsies even with normal-appearing mucosa)

Special Populations

Crohn's Disease with Persistent Diarrhea

• Consider SeHCAT testing in patients with small intestinal Crohn's disease without objective evidence of active inflammation who have persistent diarrhea 1
• Treat underlying remediable causes (active Crohn's, microscopic colitis, SIBO) in addition to BAD therapy 1

Atypical Features Suggesting Organic Disease

Consider bile acid malabsorption when: 3, 2

• Nocturnal diarrhea (alarm feature suggesting organic disease)
• Watery diarrhea worsening after meals
• Prior cholecystectomy or ileal resection
• Symptoms refractory to standard IBS-D therapy

Treatment Monitoring and Referral

Review treatment efficacy after 3 months and discontinue ineffective medications 4

Refer to gastroenterology when: 3

• Diagnostic uncertainty remains after initial evaluation
• Red flag symptoms present
• Symptoms severe or refractory to first-line treatments for 12 months
• Psychological therapies (cognitive behavioral therapy, gut-directed hypnotherapy) needed for persistent symptoms despite pharmacological treatment

Critical Pitfalls to Avoid

• Do not rely on symptom presentation alone to diagnose BAD, as no symptoms reliably predict this diagnosis 1
• Avoid codeine and opioids for chronic diarrhea management due to risks of sedation, dependency, and complications 4
• Do not use stool weights (≥200 g/day) as the primary definition of diarrhea, as normal stool volumes can exceed this with non-Western diets; instead use Bristol stool chart type 5 and above 1
• Do not assume Rome IV criteria exclude organic disease, as these have only 52-74% specificity and do not reliably exclude IBD, microscopic colitis, or BAD 1