What are the causes of diarrhea?

Causes of Diarrhea

Diarrhea has numerous causes ranging from infectious agents to non-infectious conditions affecting the gastrointestinal tract, with treatment approaches varying based on the underlying etiology. Understanding these causes is essential for appropriate management and reducing morbidity and mortality.

Infectious Causes

Viral Pathogens

• Rotavirus: Most common cause of acute diarrhea in children, accounting for approximately 25% of cases 1
• Norovirus: Common cause of outbreaks in healthcare settings and long-term care facilities 1
• Other viruses: Norwalk-like viruses, enteric adenoviruses, astroviruses, and caliciviruses 1

Bacterial Pathogens

• Salmonella, Shigella, Campylobacter, Yersinia: Important causes of inflammatory diarrhea 1
• Escherichia coli strains: Including enterotoxigenic (ETEC), enteropathogenic (EPEC), and enteroaggregative (EAEC) strains 1
• Clostridium difficile: Particularly important in patients with recent antibiotic exposure or healthcare facility exposure 1
• Vibrio species: Associated with seafood consumption and water exposure 1

Parasitic Pathogens

• Common protozoa: Giardia, Cryptosporidium, Cyclospora, and Entamoeba histolytica 1
• Microsporidia: More common in immunocompromised hosts 1
• Other parasites: Cystoisospora belli (formerly Isospora belli) 1

Non-Infectious Causes

Gastrointestinal Disorders

• Inflammatory bowel disease: Ulcerative colitis and Crohn's disease 1
• Microscopic colitis: Including collagenous and lymphocytic colitis 1
• Neoplasia: Colonic and small bowel tumors 1
• Malabsorption syndromes: Celiac disease, tropical sprue, Whipple's disease 1

Endocrine and Metabolic Causes

• Thyroid disorders: Hyperthyroidism 1
• Diabetes mellitus: Often due to autonomic neuropathy 1
• Adrenal disorders: Addison's disease 1
• Hormone-secreting tumors: VIPoma, gastrinoma, carcinoid 1

Medication-Related Causes

• Antibiotics: Disruption of normal gut flora 1
• Magnesium-containing products: Common in over-the-counter medications 1
• Other medications: Antihypertensives, non-steroidal anti-inflammatory drugs, theophyllines, antiarrhythmics, and antineoplastic agents 1

Surgical and Anatomical Causes

• Post-surgical changes: Small bowel resections, internal fistulae 1
• Post-cholecystectomy diarrhea: Occurs in up to 10% of patients due to increased gut transit, bile acid malabsorption, and increased enterohepatic cycling of bile acids 1, 2

Other Causes

• Alcohol consumption: Causes rapid gut transit, decreased intestinal disaccharidase activity, and decreased pancreatic function 1
• Food additives: Sorbitol and fructose can cause osmotic diarrhea 1
• Lactase deficiency: Leading to lactose intolerance 1
• Bile acid malabsorption: Can occur as a primary disorder or secondary to ileal disease or resection 1
• Small bowel bacterial overgrowth: Often secondary to anatomical abnormalities or motility disorders 1
• Factitious diarrhea: Self-induced or fabricated diarrhea 1

Special Considerations

Immunocompromised Patients

Immunocompromised individuals are at higher risk for severe, chronic, or relapsing diarrhea from:

• HIV-associated pathogens: Cryptosporidium, microsporidia, Cystoisospora belli, CMV, and Mycobacterium avium complex 1
• Transplant recipients: Chronic and severe norovirus infection has been reported 1
• Primary immunodeficiencies: Can lead to persistent rotavirus diarrhea 1

Traveler's Diarrhea

• Majority is self-limited and caused by bacterial pathogens 1
• Approximately 10% is caused by parasitic infections, with giardiasis being most common 1
• C. difficile is increasingly recognized in travelers with persistent diarrhea, especially those with recent antibiotic use 1

Diagnostic Approach

For chronic diarrhea (lasting >4 weeks), initial screening should include:

• Blood tests: ESR, CBC, albumin (abnormalities suggest organic disease) 1
• Serological testing for celiac disease (IgA anti-tissue transglutaminase antibodies) 1
• Stool studies for infectious causes when indicated 1

For acute infectious diarrhea, diagnostic testing should be targeted based on:

• Presence of blood in stool
• Severity of illness
• Immunocompromised status
• Recent travel history
• Known outbreaks 1

Management Considerations

Treatment should be tailored to the underlying cause:

• Infectious diarrhea: Often self-limiting; rehydration is the mainstay of treatment 3
• Chronic conditions: Specific therapy directed at underlying cause 1
• Post-cholecystectomy diarrhea: May respond to bile acid sequestrants like cholestyramine 1, 2

Pitfalls and Caveats

1. Not all diarrhea requires extensive diagnostic workup - most acute cases are self-limiting
2. Multipathogen nucleic acid amplification tests can detect multiple pathogens simultaneously, but clinical correlation is essential as not all detected pathogens may be clinically relevant 1
3. Chronic diarrhea in immunocompromised patients requires specialized testing beyond routine stool studies 1
4. Medication-induced diarrhea is common (up to 4% of chronic cases) and often overlooked 1
5. Recent antibiotic therapy should raise suspicion for C. difficile infection 1, 4

By systematically evaluating the potential causes of diarrhea based on clinical presentation, duration, and patient factors, clinicians can determine the appropriate diagnostic approach and treatment strategy to minimize morbidity and mortality.