What are the causes of chronic diarrhea?

Causes of Chronic Diarrhea

Chronic diarrhea has numerous causes that can be categorized into colonic, small bowel, pancreatic, endocrine, and other etiologies, with specific risk factors helping to determine the underlying pathology. 1

Classification of Chronic Diarrhea

Chronic diarrhea is defined as predominantly loose stools lasting longer than four weeks 2. The causes can be organized into the following categories:

1. Colonic Causes

• Colonic neoplasia - requires colonoscopy for diagnosis
• Inflammatory bowel disease (ulcerative colitis and Crohn's disease)
• Microscopic colitis - common in older adults, presents as watery diarrhea 1

2. Small Bowel Causes

• Celiac disease - characterized by malabsorption, weight loss, and iron deficiency anemia 3
• Crohn's disease - can affect any part of the GI tract
• Small bowel enteropathies (Whipple's disease, tropical sprue, amyloid, intestinal lymphangiectasia)
• Bile acid malabsorption - typically occurs after meals, responds to bile acid sequestrants 1
• Disaccharidase deficiency - including lactase deficiency
• Small bowel bacterial overgrowth - common after surgery or in motility disorders
• Mesenteric ischemia
• Radiation enteritis
• Lymphoma
• Giardiasis and other chronic infections 1

3. Pancreatic Causes

• Chronic pancreatitis
• Pancreatic carcinoma
• Cystic fibrosis 1

4. Endocrine Causes

• Hyperthyroidism
• Diabetes mellitus - can cause diarrhea through autonomic neuropathy
• Hypoparathyroidism
• Addison's disease
• Hormone-secreting tumors (VIPoma, gastrinoma, carcinoid) 1

5. Other Causes

• Factitious diarrhea - including laxative abuse
• Surgical causes (small bowel resections, internal fistulae)
• Medications - up to 4% of chronic diarrhea cases 1
• Alcohol abuse
• Autonomic neuropathy 1
• Diet-related - excessive caffeine, FODMAPs, food additives 1

Pathophysiologic Classification

Chronic diarrhea can also be categorized by mechanism 2, 4, 3:

1. Watery Diarrhea

• Secretory diarrhea - persists during fasting, caused by bile acid malabsorption, microscopic colitis, endocrine disorders
• Osmotic diarrhea - improves with fasting, caused by carbohydrate malabsorption, laxative abuse
• Functional diarrhea - including irritable bowel syndrome (most common cause of functional diarrhea) 3

2. Fatty Diarrhea (Malabsorption/Maldigestion)

• Characterized by steatorrhea, weight loss, excess gas
• Includes celiac disease, giardiasis, pancreatic exocrine insufficiency 2

3. Inflammatory Diarrhea

• Characterized by blood and pus in stool, elevated fecal calprotectin
• Includes inflammatory bowel disease, C. difficile infection, colitis 3

Key Risk Factors to Assess

When evaluating chronic diarrhea, important risk factors to consider include:

1. Family history - particularly of neoplastic, inflammatory bowel, or celiac disease 1

2. Previous surgery - especially:

   • Ileum and right colon resections (causing fat/carbohydrate malabsorption)
   • Gastric surgery (bacterial overgrowth)
   • Terminal ileum resections (bile acid diarrhea)
   • Cholecystectomy (affects up to 10% of patients) 1

3. Previous pancreatic disease 1

4. Systemic diseases - thyrotoxicosis, diabetes mellitus, adrenal disease, systemic sclerosis 1

5. Alcohol consumption - causes diarrhea through multiple mechanisms:

   • Direct toxic effect on intestinal epithelium
   • Rapid gut transit
   • Decreased intestinal disaccharidase activity
   • Decreased pancreatic function 1

6. Medication use - particularly:

   • Magnesium supplements
   • Antihypertensives (ACE inhibitors)
   • NSAIDs
   • Dipeptidyl peptidase-4 inhibitors (gliptins)
   • Antineoplastic agents
   • Theophyllines
   • Antibiotics
   • Antiarrhythmics 1

7. Recent travel history - for infectious causes 1

8. Recent antibiotic use - particularly for C. difficile infection 1

9. Dietary factors - caffeine, lactose in lactase-deficient patients, sorbitol, fructose, and FODMAPs 1

Clinical Pearls and Pitfalls

• Symptoms suggestive of organic disease include diarrhea of less than 3 months' duration, predominantly nocturnal or continuous diarrhea, and significant weight loss 1

• Malabsorption typically presents with steatorrhea (bulky, malodorous, pale stools), but milder forms may not show obvious stool abnormalities 1

• Colonic/inflammatory diarrhea typically presents with liquid loose stools containing blood or mucus 1

• C. difficile infection should be considered in patients with recent antibiotic exposure, even in outpatient settings 1

• Functional disorders like irritable bowel syndrome are common causes of chronic diarrhea but should remain a diagnosis of exclusion after organic causes are ruled out 2, 3

• When evaluating chronic diarrhea, attempt to categorize it by type (watery, fatty, or inflammatory) before extensive testing, as this narrows diagnostic possibilities and reduces unnecessary testing 3