What are the potential causes of diarrhea in various populations, including infants, elderly individuals, and those with underlying health conditions?

Causes of Diarrhea

Diarrhea results from infectious agents (viral, bacterial, parasitic, fungal), medications, underlying medical conditions, and dietary factors, with the specific etiology varying significantly by patient age, immune status, and clinical presentation. 1

Infectious Causes

Viral Pathogens

• Norovirus is the most common cause of diarrheal disease outbreaks, accounting for 58% of all foodborne gastroenteritis illnesses and causing nearly 1 million ambulatory care visits annually in children under 5 years 1, 2
• Rotavirus remains significant in unvaccinated populations, historically causing 3 million annual episodes before vaccine introduction 1, 2
• Viral pathogens typically cause watery, non-bloody diarrhea 3

Bacterial Pathogens

• Salmonella enterica subspecies (11% of illnesses but 35% of hospitalizations and 28% of deaths) is the leading bacterial cause of severe outcomes 1
• Campylobacter jejuni causes inflammatory diarrhea with fever (59% of cases), abdominal tenderness (45%), and bloody stools (52% visible blood, 37% occult blood) 1
• Shigella presents with dysentery (fever, tenesmus, blood/pus in stool) in 79% of cases, with 51% reporting bloody stools 1
• Shiga toxin-producing E. coli (STEC) O157 causes severe bloody diarrhea (91% report blood in stool, 63% visible blood) with right-sided abdominal pain but typically without fever 1, 3
• Yersinia enterocolitica causes bloody diarrhea, nonbloody diarrhea, or febrile pseudoappendicular syndrome, particularly in young African American and Asian children during winter months, diabetics, and those with chronic liver disease or iron-overload states 1, 3
• Clostridium difficile causes diarrhea following antibiotic disruption of commensal colonic bacteria, especially in elderly patients on chemotherapy or with multiple diseases 1, 4

Parasitic Pathogens

• Giardia, Cryptosporidium, and Cyclospora are the most common parasitic causes, with Cryptosporidium particularly severe in immunocompromised patients with impaired cell-mediated immunity 1, 2, 5
• Entamoeba histolytica causes amoebic dysentery with bloody diarrhea and more indolent onset 3
• Microsporidia and Cystoisospora belli (formerly Isospora belli) cause severe, chronic, or relapsing diarrhea in HIV-infected patients with advanced disease 1

Fungal and Opportunistic Pathogens in Immunocompromised Patients

• Cytomegalovirus (CMV) enteritis requires colonoscopy with biopsy for diagnosis in HIV-infected patients 1
• Mycobacterium avium complex (MAC) requires blood cultures for diagnosis 1
• Enteroaggregative E. coli causes diarrhea in HIV-associated immune compromise 1

Medication-Induced Diarrhea

Drugs account for up to 4% of chronic diarrhea cases and 7% of all drug adverse effects, with over 700 medications implicated. 1, 6

High-Risk Medications

• Antibiotics are responsible for 25% of drug-induced diarrhea through disruption of commensal bacteria 1, 4, 6
• Magnesium-containing antacids cause osmotic diarrhea 1, 4, 6
• Nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive medications are common culprits 1, 4, 6
• Proton pump inhibitors and H2-blockers decrease gastric acid production, compromising the stomach's "self-sterilizing" function and increasing infection risk 4
• Chemotherapy agents, antiarrhythmics, theophyllines, and antineoplastic agents frequently cause diarrhea 1, 6
• Prostaglandins (misoprostol), colchicine, and cholinergic agents cause secretory diarrhea 4, 6
• Sorbitol and fructose in food additives and liquid pharmaceutical preparations cause osmotic diarrhea 1, 4

Mechanisms of Drug-Induced Diarrhea

• Secretory mechanisms: Drugs activate adenylate cyclase, increasing cyclic AMP and causing active chloride/bicarbonate secretion (bisacodyl, misoprostol, chenodeoxycholic acid) 4
• Osmotic mechanisms: Poorly absorbed substances draw water into the intestinal lumen (magnesium antacids, lactulose, sorbitol) 4, 6
• Mucosal damage: Direct intestinal injury (neomycin, colchicine, gold salts, penicillamine) 4, 6
• Altered motility: Hypomotility causes bacterial overgrowth and bile salt deconjugation; hypermotility from cholinergic effects 4, 6

Underlying Medical Conditions

Gastrointestinal Disorders

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) causes chronic inflammatory diarrhea 1
• Microscopic colitis presents with chronic watery diarrhea 1
• Celiac disease causes malabsorptive diarrhea with steatorrhea 1
• Bile acid malabsorption occurs after terminal ileum resection (<100 cm) or cholecystectomy (10% of patients), typically postprandial and responsive to cholestyramine 1
• Small bowel bacterial overgrowth follows gastric surgery, jejunoileal bypass, or conditions causing hypomotility 1
• Disaccharidase deficiency (lactose intolerance) causes osmotic diarrhea 1, 7
• Chronic pancreatitis, pancreatic carcinoma, and cystic fibrosis cause fat malabsorption 1

Endocrine Disorders

• Hyperthyroidism increases intestinal motility 1
• Diabetes mellitus causes diarrhea through autonomic neuropathy 1
• Addison's disease and hypoparathyroidism alter electrolyte balance 1
• Hormone-secreting tumors (VIPoma, gastrinoma, carcinoid) cause secretory diarrhea 1

Systemic Conditions

• AIDS and immunosuppressive medications predispose to opportunistic infections and chronic diarrhea 1
• Chronic liver disease (cirrhosis, alcoholic liver disease, hepatitis) increases risk of invasive noncholera vibriosis, especially Vibrio vulnificus 1
• Iron overload states (hemochromatosis, hemolytic anemia, chronic renal failure) increase Vibrio infection risk 1
• Prior gastrectomy causes rapid transit, decreased absorptive surface, and bacterial overgrowth 1

Dietary and Environmental Factors

Food-Related Causes

• Consumption of unsafe foods: Raw meats, eggs, shellfish, unpasteurized milk or juices 1
• Contaminated water: Swimming in or drinking untreated fresh surface water from lakes or streams 1
• Food additives: Sorbitol and fructose cause osmotic diarrhea 1
• Alcohol abuse: Causes rapid gut transit, decreased disaccharidase activity, and decreased pancreatic function 1

Epidemiological Risk Factors

• Travel to developing areas increases exposure to endemic pathogens 1
• Day-care center attendance or employment facilitates person-to-person transmission 1
• Farm visits, petting zoos, or contact with reptiles or pets with diarrhea expose to zoonotic pathogens 1
• Receptive anal intercourse or oral-anal sexual contact increases risk of enteric infections 1
• Food-handler or caregiver occupation poses transmission risk 1

Population-Specific Considerations

Infants and Young Children

• Rotavirus and norovirus are the leading viral causes, with norovirus now predominant post-vaccine era 1, 2
• Salmonella (42%), Campylobacter (28%), Shigella (21%), Yersinia (5%), and E. coli O157 (3%) are the most common bacterial pathogens 1, 2
• Enteroaggregative E. coli causes serious long-term sequelae including malnutrition and growth impairment, even after infection clearance 8
• Risk of death is increased among African American infants and those with prematurity, low birth weight, less maternal education, and low income 1

Elderly Individuals

• Norovirus causes 20-30% increased risk of death and hospitalization during outbreaks in long-term care facilities for those >90 years 1
• Drug-induced diarrhea is particularly common due to polypharmacy for multiple chronic diseases 4
• Decreased gastric acid production compromises the stomach's protective barrier against pathogens 4
• Reduced T-cell quality and secretory IgA production impairs immune defense 4
• Invasive nontyphoidal salmonellosis or yersiniosis can cause mycotic aneurysms of the aorta and aortitis 1

Immunocompromised Patients

• Broad spectrum of bacterial, viral, parasitic, and fungal pathogens depending on underlying immune status 1
• HIV-infected patients require testing for enteroaggregative E. coli, Cryptosporidium, microsporidia, Cystoisospora belli, CMV, and MAC 1
• Organ transplant recipients on immunosuppression experience chronic and severe norovirus infection 1
• Noninfectious etiologies including antiretroviral therapy or chemotherapy adverse effects must be considered 1

Post-Infectious Sequelae

Post-Infectious Irritable Bowel Syndrome (PI-IBS)

• 10% of patients develop PI-IBS within 12 months after infectious gastroenteritis, increasing to 14.5% beyond one year 8
• 4.2-fold increased risk of developing IBS compared to uninfected individuals within the first year, decreasing to 2.3-fold beyond 12 months 8
• Mechanisms include persistent gut microbiota dysbiosis, increased visceral sensitivity, and ongoing mucosal inflammation with elevated intraepithelial lymphocytes and mast cells 8

Other Long-Term Complications

• Guillain-Barré syndrome, reactive arthritis, and post-infectious functional dyspepsia can be triggered by enteric infections 8
• Chronic malnutrition and growth impairment particularly following enteroaggregative E. coli infections in children 8

Clinical Pitfalls and Caveats

• Drug history is critical: Always inquire about recent antibiotics, antacids, anti-motility agents, and all medications including over-the-counter products 1
• Timing matters: Drug-induced diarrhea can appear months to years after starting therapy, making the relationship difficult to establish 6
• Request specific testing: Microscopic examination for ova and parasites typically does not include Cryptosporidium or Cyclospora testing—clinicians must specifically request these 1
• Consider HIV testing: In patients with diarrhea lasting ≥30 days, HIV testing may be appropriate 1
• Elderly vulnerability: Extremes of age predispose to infectious diarrhea and severe outcomes 1, 4