What is the diagnosis and treatment for a patient with a 3-year history of chronic diarrhea, recently worsened to include nocturnal diarrhea, characterized by 1-7 episodes of watery diarrhea per night, often with a trickle in spurts, requiring straining for complete expulsion, and accompanied by a fluttering sensation and audible gurgling in the bowels throughout the day?

Diagnosis: Likely Bile Acid Diarrhea or Microscopic Colitis

This patient's nocturnal diarrhea is an atypical feature that mandates exclusion of organic disease—specifically bile acid malabsorption and microscopic colitis—before considering a diagnosis of IBS-D. 1

Why This Is NOT Typical IBS

While the 3-year history of chronic diarrhea with bowel gurgling might initially suggest IBS-D, several red flags indicate organic pathology:

• Nocturnal diarrhea is atypical for IBS and should prompt investigation for microscopic colitis or bile acid malabsorption 1
• The need to "bear down" and expel liquid in spurts suggests overflow or incomplete evacuation patterns not typical of functional disorders 1
• True IBS rarely awakens patients from sleep with diarrhea 1

Immediate Diagnostic Workup Required

First-Line Blood Tests

• Complete blood count, C-reactive protein or ESR 1
• Celiac serology (anti-tissue transglutaminase IgA with total IgA) 1, 2
• Comprehensive metabolic panel including albumin 1
• Thyroid function tests 1

Critical Next Step: Colonoscopy with Biopsies

Colonoscopy is mandatory in this patient due to atypical features, specifically to exclude microscopic colitis. 1 Risk factors present include:

• Nocturnal or severe watery diarrhea 1
• Duration suggesting possible progression of disease 1

The British Society of Gastroenterology specifically states that colonoscopy should be performed in IBS-D patients with nocturnal diarrhea to exclude microscopic colitis, as random colonic biopsies are required for diagnosis 1

Bile Acid Malabsorption Testing

Given the nocturnal diarrhea pattern, testing for bile acid malabsorption is essential. 1, 3 Options include:

• 23-seleno-25-homotaurocholic acid (SeHCAT) scanning (if available) 1
• Serum 7α-hydroxy-4-cholesten-3-one (7αC4) 1

This is particularly important as bile acid diarrhea is a common, treatable cause of chronic diarrhea that mimics IBS-D 1

Stool Studies

• Fecal calprotectin to exclude inflammatory bowel disease 1, 2
• Stool for ova and parasites (particularly Giardia) 1

Treatment Algorithm Based on Findings

If Microscopic Colitis Confirmed

• Budesonide is first-line therapy 1
• Avoid NSAIDs, PPIs, SSRIs if possible (common precipitants) 1

If Bile Acid Malabsorption Confirmed

• Cholestyramine or colesevelam as bile acid sequestrants 1, 3
• Start at low doses and titrate up 3

If All Testing Negative (Functional Diarrhea/IBS-D)

Only after organic causes excluded:

First-line pharmacologic therapy:

• Loperamide 2-4 mg up to four times daily to reduce stool frequency and urgency 1, 4

Second-line options if loperamide insufficient:

• Tricyclic antidepressants (amitriptyline 10 mg at bedtime, titrate slowly) for global symptoms and abdominal pain 1, 4
• Ondansetron 4 mg once daily (can titrate to 8 mg three times daily) as highly efficacious 5-HT3 antagonist 4

Dietary interventions:

• Low FODMAP diet supervised by trained dietitian 1, 3
• Soluble fiber (ispaghula 3-4 g/day, gradually increased) 1

Common Pitfalls to Avoid

• Do not diagnose IBS-D in the presence of nocturnal diarrhea without excluding organic disease 1
• Do not skip colonoscopy with biopsies—microscopic colitis requires histologic diagnosis and cannot be identified by visual inspection alone 1
• Do not assume all chronic diarrhea is IBS—up to 30-40% of patients referred with presumed IBS-D have bile acid malabsorption 1
• The "trickle in spurts" pattern and need to strain suggests this may not be simple watery diarrhea and warrants thorough evaluation 1