What is the diagnostic and treatment approach for a patient presenting with chronic diarrhea?

Diagnostic and Treatment Algorithm for Chronic Diarrhea

The evaluation of chronic diarrhea requires a systematic approach beginning with categorization of diarrhea type, followed by targeted testing to determine the specific etiology, and then implementing appropriate treatment based on the identified cause. 1

Initial Assessment

Definition and Classification

• Chronic diarrhea: Abnormal passage of ≥3 loose stools per day for more than 4 weeks 1
• Categories of diarrhea:
  • Watery (secretory, osmotic, functional)
  • Fatty (malabsorption)
  • Inflammatory

Key History Elements

• Stool characteristics (consistency, frequency, volume, presence of blood/mucus)
• Nocturnal diarrhea (suggests organic disease)
• Weight loss (suggests malabsorption or inflammatory conditions)
• Medication history (antibiotics, laxatives, etc.)
• Travel history
• Family history (IBD, celiac disease, colorectal cancer)
• Surgical history (especially bowel resections)
• Diet history (food intolerances, excessive caffeine/alcohol)
• Systemic symptoms (fever, joint pain, rash)

First-Line Investigations (Primary Care)

Blood Tests

• Full blood count
• Ferritin
• C-reactive protein
• Thyroid function tests
• Tissue transglutaminase antibody (TTG IgA) and total IgA 1
• Basic metabolic panel

Stool Tests

• Fecal calprotectin or lactoferrin (to screen for IBD) 1
• Stool test for Giardia (antigen detection or PCR) 1
• C. difficile testing if recent antibiotic use 1

Categorization and Further Testing

For Watery Diarrhea

1. Functional diarrhea/IBS-D:

   • Diagnosis of exclusion after negative testing
   • Rome criteria (pain relieved by defecation, associated with change in stool form/frequency)

2. Secretory diarrhea:

   • Consider bile acid malabsorption (SeHCAT test in Europe; trial of bile acid sequestrants in North America) 1
   • Consider microscopic colitis in older patients (colonoscopy with biopsies)
   • Consider endocrine disorders (thyroid function, diabetes)

3. Osmotic diarrhea:

   • Stool osmotic gap measurement
   • Carbohydrate malabsorption tests (lactose, fructose breath tests)
   • Screen for laxative abuse

For Fatty Diarrhea (Malabsorption)

1. Small bowel disease:

   • Celiac disease: TTG IgA and total IgA; duodenal biopsies if serology negative but high suspicion 1
   • Small bowel bacterial overgrowth: Hydrogen breath tests or jejunal aspirate culture 1

2. Pancreatic insufficiency:

   • Fecal elastase test (preferred over fecal fat) 1

For Inflammatory Diarrhea

1. Colonoscopy with biopsies for:

   • IBD (Crohn's disease, ulcerative colitis)
   • Microscopic colitis
   • Colorectal cancer

2. Stool studies:

   • Fecal calprotectin/lactoferrin
   • Stool culture for invasive bacteria
   • Ova and parasites only if travel history to high-risk areas 1

Special Considerations

Age-Stratified Approach

• Patients >45 years: Full colonic imaging (preferably colonoscopy) 1
• Patients <45 years without alarm features: Flexible sigmoidoscopy may be sufficient 1

Alarm Features Requiring Urgent Evaluation

• Blood in stool
• Unintentional weight loss
• Nocturnal symptoms
• Fever
• Family history of colorectal cancer
• New onset in older adults (>50 years)

Treatment Approach

Symptomatic Management

• Antidiarrheal agents (loperamide, diphenoxylate-atropine) for symptom control
  • For chronic diarrhea: Initial dose of diphenoxylate 20 mg/day (two tablets four times daily), then reduce as control is achieved 2
  • If no improvement after 10 days at maximum dose, symptoms unlikely to respond to continued treatment 2

Specific Treatments Based on Diagnosis

1. Inflammatory conditions:

   • IBD: Anti-inflammatory medications, immunomodulators, biologics
   • Microscopic colitis: Budesonide

2. Malabsorptive conditions:

   • Celiac disease: Strict gluten-free diet
   • Bile acid malabsorption: Bile acid sequestrants (cholestyramine)
   • Pancreatic insufficiency: Pancreatic enzyme replacement

3. Functional diarrhea/IBS-D:

   • Dietary modifications (low FODMAP diet)
   • Antispasmodics
   • Antidepressants (TCAs, SSRIs) for visceral hypersensitivity

Management of Undiagnosed Cases

When extensive investigations fail to yield a diagnosis (approximately one-third of cases) 1:

1. Reassess all previous test results
2. Consider empiric trials of therapy:
   • Trial of bile acid sequestrants
   • Trial of antibiotics for bacterial overgrowth
   • Trial of elimination diets
3. Consider symptomatic management if prognosis appears good

Common Pitfalls to Avoid

1. Misdiagnosing IBS without excluding organic disease - Always perform basic screening tests
2. Missing celiac disease - Test both TTG IgA and total IgA; consider duodenal biopsies if high suspicion despite negative serology
3. Overlooking microscopic colitis - Ensure colonoscopic biopsies are taken even if mucosa appears normal
4. Failing to recognize bile acid malabsorption - Consider empiric trial of bile acid sequestrants when tests are unavailable
5. Inadequate follow-up - Clinical improvement should be seen within 48 hours for acute causes and within 10 days for chronic causes when treated appropriately 2