What are the differential diagnoses and management approaches for acute diarrhea?

Differential Diagnoses for Acute Diarrhea

Acute diarrhea has three primary categories of infectious causes—viral, bacterial, and parasitic—with distinct clinical presentations that guide diagnostic and management decisions. 1

Clinical Classification and Etiologies

Infectious Causes

Viral Diarrhea (Most Common)

• Norovirus is the leading cause of acute gastroenteritis in the United States, accounting for 58% of cases, particularly in adults 1
• Rotavirus was historically the most common pathogen in children <5 years before vaccine introduction, now superseded by norovirus 1
• Viral diarrhea typically presents as acute watery diarrhea without blood, often with vomiting, and is self-limited 1, 2
• Enteric adenoviruses may not be recovered in routine viral culture 1

Bacterial Diarrhea

• Common pathogens include: Salmonella (11% of cases), Campylobacter, Shigella, Shiga toxin-producing E. coli (STEC), and Yersinia 1, 3
• Bacterial diarrhea presents acutely with visible blood in stool, high fever, and pronounced systemic symptoms 4
• Campylobacter jejuni requires specific culture methods and is associated with Guillain-Barré syndrome 1, 4
• STEC O157 causes bloody diarrhea and carries risk of hemolytic uremic syndrome (HUS), particularly with Shiga toxin 2 producers 1, 4
• Shigella causes dysentery syndrome with frequent scant bloody stools, fever, abdominal cramps, and tenesmus 4
• Vibrio species should be considered with seafood or seacoast exposure 1
• Yersinia enterocolitica can mimic appendicitis with right-sided abdominal pain and may cause mycotic aneurysms in adults 1
• Clostridium difficile should be tested when diarrhea onset occurs >3 days after hospitalization or with recent antibiotic/chemotherapy use 1

Parasitic Diarrhea

• Giardia lamblia and Cryptosporidium are the most common parasitic causes, often tested together as primary parasitology examination 1
• Parasitic diarrhea is characterized by persistent or chronic presentation lasting weeks to months, with visible blood, mucus, and semiliquid consistency 4
• Entamoeba histolytica causes amebic diarrhea with persistent bloody diarrhea but lower fever than bacterial causes 4
• Cyclospora, Cystoisospora, Microsporidia should be considered in immunocompromised patients with persistent diarrhea 3
• Strongyloides detection may require Baermann technique or agar plate culture 1

Noninfectious Causes

Consider when symptoms persist ≥14 days: 1

• Inflammatory bowel disease (IBD) presents with chronic diarrhea, fatigue (50% at diagnosis), and systemic symptoms 5
• Irritable bowel syndrome (IBS) including postinfectious IBS 1
• Lactose intolerance should be reconsidered in patients not responding to initial therapy 1
• Microscopic colitis requires colonoscopy with biopsies for diagnosis 5
• Bile acid diarrhea presents with postprandial watery diarrhea 5

Risk Factors and Epidemiologic Clues

High-Risk Populations Requiring Broader Evaluation: 1

• Infants <3 months (higher risk for bacterial diarrhea and bacteremia) 4, 3
• Immunocompromised patients (HIV, chemotherapy, transplant recipients) require broad differential including opportunistic pathogens 1, 3
• Elderly patients (highest hospitalization and death rates) 1
• Patients with chronic liver disease, iron overload, or hemochromatosis (risk for invasive Vibrio vulnificus) 1

Exposure History Guides Specific Testing: 1

• Travel history: Consider enterotoxigenic E. coli, Campylobacter, Shigella, and parasites in travelers 1
• Foodborne exposure: Salmonella, STEC, Campylobacter, Vibrio 1
• Antibiotic use within 8-12 weeks: Test for C. difficile 1
• Seafood/seacoast exposure: Culture for Vibrio species 1
• Animal contact: Consider Salmonella, Campylobacter, STEC 1
• Daycare or institutional setting: Low-inoculum pathogens (Cryptosporidium, Giardia, norovirus, rotavirus, STEC, Shigella) 1
• Sexual practices (men who have sex with men): Proctoscopy may reveal herpes, gonorrhea, chlamydia, syphilis in distal 15 cm; Campylobacter, Shigella, C. difficile if extending proximally 1
• Outbreak setting: Report to health department and save isolates 1

Diagnostic Approach

Selective Testing Based on Clinical Presentation (Not Routine for All Cases): 3, 6

Indications for Stool Testing: 3

• Fever with diarrhea
• Bloody or mucoid stools
• Severe abdominal cramping or tenderness
• Signs of sepsis
• Immunocompromised status
• Recent hospitalization (>3 days prior to symptom onset)
• Persistent diarrhea >7 days
• Outbreak investigation

Optimal Specimen Collection: 3

• Single diarrheal stool specimen is optimal for laboratory diagnosis 3
• Rectal swab acceptable if timely diarrheal stool cannot be collected (for bacterial detection only) 3

Testing Strategy:

For Inflammatory/Bloody Diarrhea: 3

• Test for Salmonella, Shigella, Campylobacter, Yersinia, and STEC 3
• For STEC: Use methods detecting Shiga toxin (or genes) and distinguish O157:H7 from other serotypes 3
• Sorbitol-MacConkey agar or chromogenic agar for O157:H7 screening 3

For Immunocompromised Patients: 3

• Broad evaluation with bacterial culture, viral studies, and parasitic examination 3
• Additional testing for Cryptosporidium, Cyclospora, Cystoisospora, Microsporidia, Mycobacterium avium complex, Cytomegalovirus in AIDS patients 3

For Persistent Diarrhea (≥14 days): 1, 5

• Parasitic testing (Giardia, Cryptosporidium, Entamoeba) 5
• Consider IBD evaluation with fecal calprotectin 5
• Celiac disease screening 5

Tests NOT Recommended: 1

• Fecal leukocyte examination and stool lactoferrin (strong recommendation, moderate evidence) 1
• Serologic tests for establishing etiology (strong recommendation, low evidence) 1
• Peripheral white blood cell count for etiology determination 1

Important Testing Considerations:

• Multiplex molecular tests (MP-NAAT) detect DNA, not necessarily viable organisms—clinical correlation essential 1, 3
• All positive culture-independent tests should be cultured if public health reporting requires isolate submission or antimicrobial susceptibility testing would affect management 1, 3
• Blastocystis hominis and Dientamoeba fragilis pathogenicity remains controversial; may be relevant if symptoms persist without other pathogens 1

Special Monitoring for STEC Infections: 1

• Frequent monitoring of hemoglobin, platelets, electrolytes, BUN, and creatinine to detect early HUS manifestations (strong recommendation, high evidence) 1
• Examine peripheral blood smear for red blood cell fragments when HUS suspected (strong recommendation, high evidence) 1

Red Flags Requiring Urgent Evaluation

Immediate concerns: 5

• Blood in stool with unintentional weight loss
• Nocturnal diarrhea
• Symptoms <3 months with progressive worsening
• Signs of severe dehydration or sepsis
• Suspected HUS (bloody diarrhea with anemia, thrombocytopenia, renal dysfunction)

Common Pitfalls to Avoid

• Do not order indiscriminate stool cultures on all patients with acute diarrhea—this is costly and low-yield (historically $900-$1,000 per positive result) 7
• Do not assume functional disorder without excluding organic causes, particularly in patients with alarm features 5
• Do not delay parasitic testing in persistent diarrhea >14 days 5
• Do not use empiric antibiotics in immunocompetent patients with bloody diarrhea while awaiting results (strong recommendation) 1, 4
• Avoid antibiotics in STEC O157 and Shiga toxin 2-producing STEC due to increased HUS risk 4
• Do not miss C. difficile testing in healthcare-associated diarrhea or recent antibiotic exposure 1