What are the causes of diarrhea?

Causes of Diarrhea

Diarrhea has infectious and non-infectious causes, with the specific etiology varying by duration (acute vs. chronic), patient immune status, and epidemiologic exposures.

Infectious Causes

Viral Pathogens

• Norovirus is the most common cause of diarrheal disease outbreaks and represents a major source of acute gastroenteritis across all age groups 1
• Rotavirus is the most common cause of acute diarrhea among children, accounting for one-fourth of all pediatric cases 1
• Other viral causes include Norwalk-like viruses, enteric adenoviruses, astroviruses, and caliciviruses 1
• Rotavirus disease and hospitalizations have been reduced markedly since licensure of ACIP-recommended rotavirus vaccines 1

Bacterial Pathogens

• Important bacterial causes include Salmonella, Shigella, Yersinia, Campylobacter, and pathogenic strains of Escherichia coli (including ETEC, EPEC, EAEC, and STEC) 1
• The majority of traveler's diarrhea is caused by bacterial pathogens and, to a lesser extent, viral pathogens, typically lasting <7 days 1
• Clostridium difficile is of increasing concern, especially in travelers with recent antimicrobial therapy 1
• Vibrio vulnificus infections occur in patients with chronic liver disease, iron overload states, or other immunocompromising conditions 1

Parasitic Pathogens

• Common parasitic causes include Giardia, Cryptosporidium, and Entamoeba histolytica 1
• Approximately 10% of traveler's diarrhea is caused by parasitic infections, which can persist for weeks to months, with giardiasis being the most common 1
• Cyclospora and Cystoisospora (formerly Isospora belli) are additional parasitic causes 1

Non-Infectious Causes

Medication-Induced

• Up to 4% of chronic diarrhea cases are medication-induced, particularly from magnesium-containing products, antihypertensives, NSAIDs, antibiotics, and antiarrhythmics 2
• Adverse effects of antiretroviral therapy or chemotherapy may account for persistent diarrhea in immunocompromised hosts 1

Malabsorptive Disorders

• Chronic pancreatitis is a primary cause of steatorrhea presenting as pale, bulky, malodorous stools due to inadequate fat digestion 2
• Pancreatic carcinoma and cystic fibrosis similarly impair pancreatic enzyme secretion, leading to fat malabsorption 2
• Celiac disease is the most common small bowel enteropathy in Western populations, frequently presenting with steatorrhea 2
• Bile acid malabsorption produces diarrhea that characteristically occurs after meals and typically responds to fasting, particularly common after terminal ileum resection or cholecystectomy 2

Endocrine and Metabolic

• Hyperthyroidism causes diarrhea through endocrine effects on gut motility 2
• Diabetes mellitus causes diarrhea via multiple mechanisms: autonomic neuropathy, bacterial overgrowth, bile acid malabsorption, and medication effects 2

Factitious Diarrhea

• Factitious diarrhea represents 20% of cases at tertiary referral centers, making it the most common cause of diarrhea of previously undetermined origin 3
• In patients who have undergone extensive evaluation, 33% were found to be taking laxatives or diuretics 3
• A measured stool osmolality significantly below normal plasma osmolality (200 vs. 290 mosmol/L) indicates dilutional factitious diarrhea 3

Special Populations

Immunocompromised Patients

• Diarrhea in immunocompromised patients may involve bacterial, viral, parasitic, and fungal pathogens depending on underlying immune status 1
• HIV-infected patients are at risk for enteroaggregative E. coli, Cryptosporidium, microsporidia, Cystoisospora belli, CMV, and Mycobacterium avium complex (MAC) 1
• Diarrhea caused by Cryptosporidium, Cyclospora, Cystoisospora, or microsporidia is more likely to be severe, chronic, or relapsing in immunocompromised people, particularly those with impaired cell-mediated immunity 1
• Chronic and severe norovirus infection has been reported in patients receiving immunosuppression following organ transplantation 1

High-Risk Groups for Specific Pathogens

• Risk factors for invasive nontyphoidal Salmonella infection include young and advanced age, HIV infection, cytotoxic chemotherapy, malnutrition, hemoglobinopathies, recent malaria, and cirrhosis 1
• Yersinia enterocolitica higher risk groups include young African American and Asian children (especially during winter), diabetics, and those with chronic liver disease, malnutrition, or iron-overload states 1

Clinical Pitfalls

• Microscopic examination of stool for ova and parasites is unlikely to include testing for Cryptosporidium and Cyclospora; clinicians should specifically request these tests 1
• In patients with diarrhea lasting ≥30 days, testing for HIV may be appropriate 1
• Normal vital signs and physical examination despite reported severe symptoms are consistent with factitious diarrhea 3
• Multipathogen nucleic acid amplification tests can detect multiple pathogens simultaneously, but the clinical significance of detecting multiple pathogens or nucleic acid alone (versus viable organisms) remains unclear 1