What is the differential diagnosis and treatment for a patient presenting with loose stools, abdominal pain, high-grade fever, and headache?

Differential Diagnosis for Loose Stools, Abdominal Pain, High-Grade Fever, and Headache

The combination of loose stools, abdominal pain, high-grade fever, and headache most strongly suggests acute bacterial gastroenteritis, particularly Campylobacter, Salmonella, Shigella, or Yersinia species, which characteristically present with this constellation of symptoms. 1, 2

Key Differential Diagnoses

Primary Bacterial Causes (Most Likely)

• Campylobacter, Salmonella, Shigella, Yersinia: These pathogens classically cause abdominal pain with high-grade fever 1, 2
• Shiga toxin-producing E. coli (STEC): Presents with severe abdominal pain and often grossly bloody stools, though patients are typically NOT febrile at presentation (important distinguishing feature) 1
• Non-cholera Vibrio species: Consider if patient has exposure to salty/brackish waters or consumed raw/undercooked shellfish 1
• Clostridioides difficile: Must be considered if recent antibiotic exposure within 8-12 weeks 1, 3

Viral Causes (Less Likely with High Fever)

• Norovirus: Typically causes vomiting and non-bloody diarrhea lasting 2-3 days with low-grade fever in only 40% during first 24 hours 1, 4
• Rotavirus: More common in children, generally causes watery diarrhea without high fever 4, 5

Parasitic Causes (If Symptoms Persist >14 Days)

• Entamoeba histolytica: Causes persistent/chronic diarrhea with visible blood and mucus, often with high fever 1, 2, 3
• Giardia, Cryptosporidium, Cyclospora: Typically cause persistent watery diarrhea without high fever 1, 4

Critical Consideration in Immunocompromised Patients

• Cytomegalovirus (CMV) colitis: Presents with diarrhea, rectal bleeding, fever, abdominal pain, and weight loss in transplant recipients, HIV patients, or those on immunosuppression 1
• Neutropenic enterocolitis/typhlitis: High mortality if misdiagnosed; requires broad-spectrum antibiotics and bowel rest 1

Diagnostic Approach

Immediate Clinical Assessment

Obtain focused history on:

• Stool characteristics: presence of blood, mucus, or watery consistency 1, 3
• Recent antibiotic use (within 8-12 weeks) to assess C. difficile risk 1, 3
• Food exposures: raw/undercooked meat, shellfish, unpasteurized dairy 1
• Travel history: recent travel to endemic areas 1, 4
• Immune status: HIV, transplant, chemotherapy, chronic steroids 1
• Outbreak setting: multiple people with similar symptoms 1

Laboratory Testing Strategy

Stool testing is indicated for:

• Fever with diarrhea (your patient qualifies) 4
• Severe abdominal cramping or tenderness (your patient qualifies) 4
• Signs of sepsis 4

Specific tests to order:

• Single diarrheal stool specimen for bacterial pathogens: Salmonella, Shigella, Campylobacter, Yersinia, and STEC 1, 4
• Molecular multiplex testing preferred over traditional stool cultures for higher sensitivity 3, 4
• C. difficile toxin testing if any antibiotic exposure in past 8-12 weeks 1
• Blood cultures if signs of septicemia or patient <3 months old 2, 4
• Stool for ova and parasites only if diarrhea persists >14 days 1

Imaging

• Contrast-enhanced CT scan is the most reliable exam if severe abdominal pain suggests complications (abscess, perforation, toxic megacolon) 1
• Plain radiographs and ultrasound are insufficiently sensitive 1

Treatment Algorithm

Immediate Management

Hydration is paramount:

• Oral rehydration solution (WHO formulation: Na 90 mM, K 20 mM, glucose 111 mM) for all patients able to take oral fluids 3
• Intravenous hydration if unable to tolerate oral intake 5

Antibiotic Therapy Decision Tree

DO NOT give empiric antibiotics while awaiting test results in immunocompetent patients with bloody diarrhea 2, 3, 4

EXCEPTIONS warranting empiric antibiotics:

• Infants <3 months with suspected bacterial etiology 2, 4
• Documented fever + abdominal pain + bloody diarrhea with presumed bacillary dysentery (Shigella) 2, 3
• Immunocompromised patients require broad-spectrum coverage 1

Antibiotic choices when indicated:

• Adults: Fluoroquinolones (ciprofloxacin) or azithromycin 2
• Children: Third-generation cephalosporins or azithromycin 2

Critical Pitfalls to Avoid

NEVER give antibiotics for STEC O157 or Shiga toxin 2-producing STEC due to increased risk of hemolytic uremic syndrome (HUS) 2, 4

Red flags requiring urgent evaluation:

• Bloody diarrhea with anemia, thrombocytopenia, or renal dysfunction (suspect HUS) 4
• Signs of toxic megacolon or peritonitis 1
• Severe dehydration or hemodynamic instability 3

Do not miss:

• C. difficile testing in healthcare-associated diarrhea 4
• CMV colitis in immunocompromised patients (requires tissue biopsy with immunohistochemistry for definitive diagnosis) 1
• Vibrio species if exposure to brackish water or raw shellfish 1

Special Population Considerations

If immunocompromised:

• Broader differential including CMV, Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex 1
• Lower threshold for imaging and endoscopy 1
• Early surgical consultation if neutropenic enterocolitis suspected 1

If recent hospitalization or antibiotics:

• C. difficile is primary concern; test immediately 1
• Consider vancomycin or fidaxomicin if severe disease 1