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

Chronic Diarrhea Workup

Definition and Initial Triage

Begin with initial non-invasive investigations in primary care, including coeliac serology, faecal calprotectin, and possibly FIT, before specialist referral. 1

Chronic diarrhea is defined as passage of ≥3 loose stools per day (Bristol stool type 5 or above) persisting for more than 4 weeks, which distinguishes it from acute infectious causes. 1, 2

Critical First Step: Identify Alarm Features

Immediately assess for alarm features that mandate urgent gastroenterology referral and colonoscopy: 2, 3

• Age ≥45 years with new-onset symptoms 1, 2
• Unintentional weight loss 2, 3
• Blood in stool (visible or occult) 2, 3
• Nocturnal diarrhea (suggests organic disease, not functional) 3
• Fever 2
• Symptoms <3 months duration (paradoxically suggests organic rather than functional disease) 3
• Family history of inflammatory bowel disease or colorectal cancer 3

First-Line Laboratory Investigations (Primary Care)

All patients require this baseline panel before specialist referral: 1, 2, 3

Blood Tests:

• Complete blood count 2, 3
• C-reactive protein 2, 3
• Comprehensive metabolic panel 2
• Liver function tests 2
• Iron studies, vitamin B12, folate 2
• Thyroid function tests 2
• Anti-tissue transglutaminase IgA WITH total IgA (critical: total IgA detects IgA deficiency that causes false-negative celiac testing) 2, 3

Stool Studies:

• Faecal calprotectin (differentiates inflammatory from non-inflammatory causes) 1, 2
• Fecal immunochemical test (FIT) for occult blood 1, 2
• Stool culture only if infectious etiology suspected based on history 2
• Giardia antigen test or PCR (sensitivity/specificity >95%) 3

Age-Stratified Endoscopic Approach

Patients ≥45 Years or With Alarm Features:

Perform full colonoscopy with biopsies from both right and left colon, regardless of other test results. 1, 2 This approach reduces missed colorectal cancer diagnoses to <1%. 1

Patients <40 Years Without Alarm Features:

Avoid immediate colonoscopy if faecal calprotectin is normal. 1, 2 Instead, consider positive diagnosis of irritable bowel syndrome using Rome IV criteria after completing basic screening. 2

Critical caveat: Rome IV criteria alone have only 52-74% specificity and do not reliably exclude inflammatory bowel disease, microscopic colitis, or bile acid diarrhea—all common and treatable conditions. 1, 3 Therefore, never diagnose IBS based on Rome criteria alone without completing the blood and stool screening first. 2

Evaluation for Specific Treatable Causes

Bile Acid Diarrhea (Commonly Missed):

All patients with persistent undiagnosed chronic diarrhea should be investigated for bile acid diarrhea. 1

High-risk patients requiring testing: 3

• History of terminal ileal resection
• Prior cholecystectomy
• Abdominal radiotherapy

Diagnostic approach: 1, 3

• Preferred: SeHCAT testing (if available)
• Alternative: Serum 7-alpha-hydroxy-4-cholesten-3-one (C4 assay)
• Last resort: Faecal bile acid measurement or empirical trial of bile acid sequestrants only when objective testing unavailable

Microscopic Colitis:

Cannot be diagnosed without histology. 2 Requires colonoscopy with biopsies from right and left colon, even if mucosa appears normal endoscopically. 1, 2

Small Bowel Bacterial Overgrowth:

When suspected, use empirical trial of antibiotics rather than routine hydrogen or methane breath testing. 1

Testing for Rare Causes

Test for hormone-secreting tumors only after excluding all other causes of diarrhea. 1 These are rare and should not be part of initial workup. 1

Common Pitfalls to Avoid

• Missing celiac disease: Forgetting to order celiac serology or missing IgA deficiency (which causes false-negative IgA-tTG results) 2, 3
• Premature IBS diagnosis: Using Rome criteria alone without completing basic blood and stool screening first 2, 3
• Missing microscopic colitis: Not performing colonoscopy with biopsies in appropriate patients 2
• Missing bile acid diarrhea: Not testing objectively in patients with risk factors (cholecystectomy, ileal resection) 2, 3
• Inadequate colonoscopy: Not obtaining biopsies from right and left colon during colonoscopy 1
• Inappropriate testing: Ordering broad ova and parasite panels in patients without travel history (extremely low yield) 3
• Medication oversight: Neglecting to review medications as potential causes (proton pump inhibitors, antibiotics, metformin) 3

Symptomatic Management While Investigating

Loperamide is first-line antidiarrheal therapy. 2, 4 Initial dose: 4 mg followed by 2 mg after each unformed stool. Average maintenance dose: 4-8 mg daily. Maximum: 16 mg daily. 4 Probiotics can be used as alternative symptomatic agent. 2