Management of Chronic Diarrhea
The management of chronic diarrhea requires a systematic diagnostic approach to identify treatable causes before initiating symptomatic therapy, with loperamide as first-line symptomatic treatment and cause-specific interventions (cholestyramine for bile acid diarrhea, gluten-free diet for celiac disease, budesonide for microscopic colitis) when a diagnosis is established. 1, 2, 3
Initial Diagnostic Evaluation
History and Risk Factor Assessment
The evaluation begins with identifying alarm features and specific risk factors that guide testing:
Screen for alarm features including blood in stool, unintentional weight loss, nocturnal diarrhea, fever, symptoms <3 months duration, or recent change in bowel habit—these suggest organic disease requiring urgent evaluation. 1, 2
Identify bile acid diarrhea risk factors including terminal ileal resection, cholecystectomy, or abdominal radiotherapy, as these strongly predict bile acid malabsorption. 1, 2
Assess medication history as up to 4% of chronic diarrhea cases are medication-induced, particularly from magnesium supplements, ACE inhibitors, NSAIDs, DPP-4 inhibitors, antibiotics, and theophyllines. 1, 3
Evaluate surgical history for extensive small bowel resections (causing malabsorption), gastric bypass procedures (predisposing to bacterial overgrowth), or shorter terminal ileal resections (causing bile acid diarrhea). 1
Review dietary triggers including excessive caffeine, alcohol, sorbitol, fructose, and FODMAPs. 1, 3
First-Line Laboratory Testing
All patients with chronic diarrhea require celiac disease screening and Giardia testing regardless of symptom presentation, as these are common and treatable causes:
IgA tissue transglutaminase with total IgA level (sensitivity and specificity >90% using thresholds of 7-15 AU/mL)—the total IgA is essential to avoid false-negatives from IgA deficiency. 2
Giardia antigen test or PCR (sensitivity and specificity >95%). 2
Complete blood count, C-reactive protein, ferritin, and albumin to screen for inflammation, anemia, and malabsorption. 1, 2
Thyroid function tests with TSH as the best predictor for hyperthyroidism. 1
Common pitfall: Ordering broad ova and parasite panels in patients without travel history has extremely low yield and should be avoided. 2
Cause-Specific Management
Bile Acid Diarrhea
For patients with positive SeHCAT testing (where available), elevated serum C4, or high-risk features (cholecystectomy, terminal ileal resection, radiotherapy):
Cholestyramine is the initial therapy of choice for bile acid malabsorption. 1, 3
Use alternate bile acid sequestrants (colestipol, colesevelam) when cholestyramine tolerability is an issue. 1
Maintenance therapy should use the lowest effective dose with a trial of intermittent on-demand dosing rather than continuous daily therapy to minimize adverse events. 1, 3
Avoid bile acid sequestrants in patients with extensive ileal Crohn's disease or resection—use alternative antidiarrheal agents instead. 1
Important caveat: Testing is preferred over empiric bile acid sequestrant therapy, though empiric trials may be considered when testing is unavailable. 1, 2
Celiac Disease
A strict lifelong gluten-free diet is mandatory once celiac disease is confirmed by positive serology and duodenal biopsy. 3
Upper endoscopy with duodenal biopsies should be performed when celiac serology is positive to confirm the diagnosis. 2
Microscopic Colitis
- Budesonide 9 mg once daily for refractory cases of inflammatory diarrhea, particularly microscopic colitis. 3
Infectious Causes
Avoid excessive antimicrobial therapy based on PCR alone without evidence of active toxin production in post-infectious IBS after C. difficile. 3
Recognize that one in four patients experience relapse or treatment failure for C. difficile infection. 3
Symptomatic Management
First-Line Pharmacological Treatment
When no specific treatable cause is identified or while awaiting diagnostic results:
Loperamide is the first-line symptomatic treatment, starting with 4 mg initially, then 2 mg every 2-4 hours or after every unformed stool, with a maximum daily dose of 16 mg. 3, 4
More potent opioids (tincture of opium, morphine, codeine) may be used if loperamide is ineffective. 3, 5, 6
Critical warning: Loperamide overdose can cause serious cardiac adverse reactions including QT prolongation and arrhythmias. 3
Dietary Modifications
Eliminate potential triggers including caffeine, alcohol, sorbitol, and fructose for symptomatic relief. 3
Consider a bland/BRAT diet (bread, rice, applesauce, toast) and reduce insoluble fiber intake. 3
Lactose restriction or lactase enzyme supplements for confirmed lactose intolerance. 3
Additional Symptomatic Agents
Cholestyramine can be used empirically for suspected bile acid diarrhea even without formal testing. 3, 5
Clonidine has proabsorptive and motility effects but its antihypertensive action limits utility. 5
Octreotide is valuable for endocrine tumor-related diarrhea and dumping syndrome but less established for nonspecific diarrhea. 5
Endoscopic Evaluation
Colonoscopy with biopsies is indicated when:
- Inflammatory markers are elevated 2
- Alarm features are present 2
- Initial testing is unrevealing but symptoms persist and impair quality of life 2
- Aim for >90% cecal intubation rate with terminal ileal intubation 2
Critical Pitfalls to Avoid
Never assume functional diarrhea based on Rome IV criteria alone—these criteria have only 52-74% specificity and cannot reliably exclude IBD, microscopic colitis, or bile acid diarrhea. 2, 3
Always screen for celiac disease and check fecal calprotectin before labeling as functional. 3
Do not miss IgA deficiency when interpreting celiac serology, as this causes false-negative IgA-tTG results. 2
Avoid chronic use of loperamide with eluxadoline due to increased constipation risk—loperamide may only be used occasionally for acute severe diarrhea with eluxadoline. 7
Review and discontinue offending medications when possible, as this is a common and reversible cause. 3