What is the appropriate workup and management for a general adult patient presenting with chronic diarrhea and abdominal pain?

Workup of Chronic Diarrhea with Abdominal Pain

Begin with targeted blood and stool testing followed by colonoscopy with biopsies if alarm features are present or initial testing is abnormal. 1, 2

Initial Clinical Assessment

Identify alarm features that mandate urgent investigation:

• Unintentional weight loss – excludes functional disorders and requires colonoscopy within 2-4 weeks 2, 3
• Nocturnal diarrhea – suggests organic disease rather than functional bowel disorder 2, 3
• Blood in stools or iron deficiency anemia – requires immediate colonoscopy to exclude inflammatory bowel disease or colorectal cancer 2, 3
• Age ≥45 years with new-onset symptoms – mandates full colonoscopy due to colorectal cancer risk 3
• Fever or persistent symptoms despite treatment – suggests inflammatory or infectious etiology 3, 4

Key historical elements to elicit:

• Medication review (up to 4% of chronic diarrhea is drug-induced, including NSAIDs, antibiotics, metformin, PPIs) 3
• Recent antibiotic use (raises suspicion for C. difficile) 3
• Family history of inflammatory bowel disease, celiac disease, or colorectal cancer 2
• Dietary triggers, particularly lactose or high-fat meals 1
• Prior abdominal surgery or radiation therapy 1, 5

First-Line Laboratory Testing

Order the following blood tests for all patients:

• Complete blood count – assess for anemia indicating celiac disease, inflammatory bowel disease, or malignancy 2, 3
• C-reactive protein or ESR – evaluate for systemic inflammation 3
• Comprehensive metabolic panel – assess electrolyte disturbances and renal function 3
• Iron studies, vitamin B12, and folate – identify malabsorption 3
• Thyroid function tests – exclude hyperthyroidism 3
• IgA tissue transglutaminase with total IgA – screen for celiac disease (higher prevalence in general population) 2, 3

Order the following stool tests:

• Fecal calprotectin or fecal lactoferrin – distinguish inflammatory from non-inflammatory causes with >90% sensitivity for inflammatory bowel disease; use threshold of 50 mg/g for calprotectin to optimize sensitivity 1, 2
• Stool culture and C. difficile toxin – exclude infectious etiology, particularly if recent antibiotic use 3, 6
• Fecal immunochemical test (FIT) – assess for occult blood loss and guide urgency of colonoscopy 1, 3
• Giardia antigen testing – common cause of chronic diarrhea with high diagnostic accuracy 2

Endoscopic Evaluation Algorithm

Age ≥45 years OR any alarm features present:

• Full colonoscopy with biopsies is mandatory within 2-4 weeks due to colorectal cancer risk 1, 3
• Obtain biopsies from right and left colon (not rectum) even if mucosa appears normal – essential to diagnose microscopic colitis, which has entirely normal-appearing mucosa on endoscopy 1, 3

Age <40 years without alarm features and normal fecal calprotectin:

• Avoid immediate colonoscopy and consider positive diagnosis of irritable bowel syndrome using Rome IV criteria after completing basic screening 1, 3
• However, if symptoms persist despite treatment or fecal calprotectin is elevated, proceed to colonoscopy 1

Elevated fecal calprotectin (>50 mg/g):

• Colonoscopy with biopsies is required regardless of age, as this indicates inflammatory bowel disease until proven otherwise 1, 3
• CT imaging is inadequate for detecting microscopic colitis, early inflammatory bowel disease, or subtle mucosal abnormalities 3

Evaluation for Common Treatable Causes

If initial workup is negative, test for bile acid diarrhea:

• SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one (depending on local availability) – make a positive diagnosis rather than empirical trial 1, 3
• In North America where SeHCAT is unavailable, an empirical trial of bile acid binders (cholestyramine) is reasonable if clinically suspected 2

If lactose maldigestion is suspected:

• Hydrogen breath testing (if available) or withdrawal of dietary lactose from the diet 1

If small bowel disease is suspected after negative colonoscopy:

• MR enterography or video capsule endoscopy – evaluate small bowel abnormalities 1
• Do not use small bowel barium follow-through due to poor sensitivity and specificity 1

If fat malabsorption is suspected:

• Fecal elastase testing – assess for pancreatic insufficiency 1

If small bowel bacterial overgrowth is suspected:

• Empirical trial of antibiotics rather than breath testing due to insufficient evidence for routine hydrogen or methane breath testing 1

Common Pitfalls to Avoid

• Premature IBS diagnosis – Rome IV criteria have only 52-74% specificity and cannot reliably exclude microscopic colitis, inflammatory bowel disease, or bile acid diarrhea without completing basic screening 3
• Missing microscopic colitis – occurs if colonoscopy with biopsies is not performed, as mucosa appears entirely normal on endoscopy 1, 3
• Missing bile acid diarrhea – occurs if objective testing is not performed 3
• Inadequate colonoscopy in older patients – can lead to missing colorectal cancer 3
• Forgetting celiac serology – leads to delayed diagnosis of celiac disease 2, 3
• Relying on CT alone – normal CT does not exclude significant colonic pathology requiring endoscopic diagnosis 3
• Repetitive testing after functional diagnosis – once functional pain is established, repetitive testing is not recommended and patient should receive psychological support 7

Symptomatic Management While Awaiting Workup

Loperamide is first-line antidiarrheal:

• Initial dose of 4 mg followed by 2 mg after each unformed stool 8
• Average maintenance dose of 4-8 mg daily for chronic diarrhea 8
• Maximum daily dose is 16 mg (eight capsules) 8
• Avoid dosages higher than recommended due to risk of serious cardiac adverse reactions 8

Ensure appropriate fluid and electrolyte replacement as needed 8