Causes of Chronic Diarrhea
Chronic diarrhea has numerous causes that can be systematically categorized into colonic, small bowel, pancreatic, endocrine, and other etiologies, with inflammatory bowel disease, microscopic colitis, and bile acid malabsorption being particularly common and treatable conditions that must not be missed. 1
Definition and Clinical Framework
Chronic diarrhea is defined as loose stools (Bristol stool chart type 5 or above) persisting for more than 4 weeks, which suggests a non-infectious etiology requiring investigation. 1 The 4-week cutoff distinguishes chronic from acute diarrhea and signals the need for systematic evaluation. 1
Major Categories of Causes
Colonic Causes
- Colonic neoplasia - must be excluded, particularly with alarm features 1
- Inflammatory bowel disease (ulcerative colitis and Crohn's colitis) - common treatable cause 1
- Microscopic colitis (collagenous and lymphocytic) - accounts for 15% of chronic diarrhea cases in adults, requires histologic diagnosis even with normal-appearing mucosa 2, 3, 4
Small Bowel Causes
- Celiac disease - most common small bowel enteropathy in Western populations, presents with malabsorption and fat-soluble vitamin deficiencies 1, 2, 3
- Crohn's disease - can affect any part of GI tract 1
- Other enteropathies including Whipple's disease, tropical sprue, amyloid, intestinal lymphangiectasia 1
- Bile acid malabsorption - relatively common and treatable, typically occurs after meals and responds to cholestyramine 1, 2, 4
- Disaccharidase deficiency (lactose intolerance) 1
- Small bowel bacterial overgrowth - particularly after gastric or bowel surgery 1, 2, 4
- Mesenteric ischemia 1
- Radiation enteritis 1
- Lymphoma 1
- Giardiasis and other chronic infections - classic infectious malabsorptive cause, particularly with travel history 1, 2, 4
Pancreatic Causes
- Chronic pancreatitis - causes pancreatic exocrine insufficiency with fat-soluble vitamin deficiencies 1, 2, 3
- Pancreatic carcinoma - must be excluded with appropriate imaging 1, 2
- Cystic fibrosis 1
Endocrine Causes
- Hyperthyroidism - common reversible cause 1, 2, 3, 4
- Diabetes mellitus - can cause diarrhea through autonomic neuropathy 1, 4
- Hypoparathyroidism 1
- Addison's disease 1, 4
- Hormone-secreting tumors (VIPoma, gastrinoma, carcinoid) 1
Other Important Causes
- Medications - up to 4% of chronic diarrhea cases, including magnesium-containing products, antihypertensives, NSAIDs, theophyllines, antibiotics, antiarrhythmics, antineoplastic agents 1
- Factitious diarrhea (laxative abuse) - must be excluded with laxative screen 1, 4
- Post-surgical causes - extensive ileal/right colon resections cause malabsorption; shorter terminal ileum resections cause bile acid diarrhea; up to 10% post-cholecystectomy 1
- Alcohol abuse - causes rapid transit, decreased disaccharidase activity, decreased pancreatic function 1
- Autonomic neuropathy 1
Critical Historical Red Flags
Alarm features indicating organic disease and requiring urgent evaluation within 2-4 weeks include: 2, 4
- Nocturnal diarrhea (awakening from sleep) - has high specificity for organic pathology and is an exclusion criterion for functional disorders like IBS 1, 2, 3, 4
- Significant weight loss - suggests malabsorption or malignancy 1
- Duration less than 3 months with continuous symptoms - more likely organic than functional 1
- Blood or mucus in stool - suggests inflammatory or colonic cause 1
- Fecal incontinence during sleep - indicates severe disease burden 4
Essential Risk Factors to Elicit
- Family history of inflammatory bowel disease, celiac disease, or neoplasia 1
- Previous surgery - ileal resection, gastric surgery, cholecystectomy 1
- Previous pancreatic disease 1, 3
- Systemic diseases - thyroid disorders, diabetes, scleroderma 1
- Recent overseas travel - suggests infectious etiology 1
- Recent antibiotic use - raises concern for Clostridium difficile 1
- Medication review - comprehensive assessment of all medications and supplements 1
Distinguishing Malabsorptive from Inflammatory Patterns
Malabsorptive diarrhea presents with bulky, malodorous, pale stools (steatorrhea), though milder forms may not show obvious stool abnormalities. 1 Fat-soluble vitamin deficiencies (A, D, E, K) and iron deficiency strongly suggest small bowel enteropathy, particularly celiac disease. 2, 3
Inflammatory/colonic diarrhea typically presents with liquid loose stools containing blood or mucus. 1
Treatment Approach by Specific Diagnosis
Treatment must be tailored to the underlying pathophysiology once identified: 4
- Celiac disease: Strict lifelong gluten-free diet 2, 3, 4
- Microscopic colitis: Budesonide 2, 4
- Bile acid diarrhea: Cholestyramine or bile acid sequestrants 2, 3, 4
- Inflammatory bowel disease: Disease-specific immunosuppressive therapy (e.g., mesalamine for ulcerative colitis) 4, 5
- Pancreatic insufficiency: Pancreatic enzyme replacement 3
- Small bowel bacterial overgrowth: Antibiotics 2, 4
- Giardiasis: Antiparasitic therapy 2
Critical Pitfalls to Avoid
- Never diagnose irritable bowel syndrome in patients with nocturnal diarrhea - this is an exclusion criterion for functional disorders and indicates organic pathology requiring full workup 2, 3, 4
- Never skip colonic biopsies even with normal-appearing mucosa - microscopic colitis requires histologic diagnosis and cannot be detected endoscopically 2, 3, 4
- Never rely on negative celiac serology alone - antibody-negative celiac disease accounts for 6.4-7% of cases; duodenal biopsies are mandatory 3
- Never use empiric loperamide until organic causes are excluded - symptomatic treatment masks the underlying diagnosis and delays appropriate therapy 2
- Never perform flexible sigmoidoscopy alone - full colonoscopy is required to evaluate the entire colon for right-sided lesions and microscopic colitis 2, 4
- Never rely on CT imaging alone - it is inadequate for detecting microscopic colitis, early IBD, or subtle mucosal abnormalities 4