What are the differential diagnoses for a patient with diarrhea and no fever?

Differential Diagnoses for Diarrhea Without Fever

In a patient with diarrhea and no fever, the differential diagnosis should prioritize viral gastroenteritis (especially norovirus), STEC infection, parasitic infections, toxin-mediated bacterial illness, and non-infectious causes including medication effects and functional disorders. 1, 2

Key Clinical Context: Absence of Fever Narrows the Differential

The absence of fever is clinically significant because it helps distinguish certain pathogens from others:

• STEC (Shiga toxin-producing E. coli) characteristically presents WITHOUT fever at the time of presentation, despite causing severe abdominal pain and often grossly bloody stools 1, 3
• Viral gastroenteritis (norovirus) typically causes low-grade or no fever, with vomiting and nonbloody diarrhea lasting 2-3 days 1, 2
• Toxin-mediated bacterial illness (Staphylococcus aureus enterotoxin, Bacillus cereus, Clostridium perfringens) presents with nausea, vomiting, and diarrhea lasting ≤24-48 hours without significant fever 1

Infectious Causes to Consider

Viral Pathogens

• Norovirus is the leading cause of acute gastroenteritis in the United States (58% of cases), presenting as acute watery diarrhea without blood, often with vomiting, and is self-limited 2
• Typically causes vomiting and nonbloody diarrhea lasting 2-3 days, with low-grade fever present in only 40% during the first 24 hours 1

Bacterial Pathogens

• STEC (especially O157:H7): Severe abdominal pain with bloody stools but minimal or no fever is the hallmark presentation 1, 3
• Toxin-mediated illness: Staphylococcus aureus or Bacillus cereus (short-incubation) cause nausea and vomiting lasting ≤24 hours; Clostridium perfringens or B. cereus (long-incubation) cause diarrhea and cramping lasting 1-2 days 1
• Vibrio species: Consider if patient consumed raw/undercooked shellfish or had exposure to brackish water, can present with large volume "rice water" stools 1, 3

Parasitic Pathogens

• Giardia lamblia and Cryptosporidium are the most common parasitic causes, presenting with persistent or chronic diarrhea (≥14 days) 1, 2
• Entamoeba histolytica: Persistent or chronic presentation with visible blood, mucus, and semiliquid consistency 1, 4
• Other parasites to consider in persistent diarrhea: Cyclospora cayetanensis, Cystoisospora belli 1

Non-Infectious Causes

Medication-Related

• Antibiotic-associated diarrhea: Test for C. difficile if antibiotic use within preceding 8-12 weeks, though C. difficile can present with or without fever 1, 2, 3
• Other medications causing diarrhea should be reviewed in the history 5, 6

Functional and Inflammatory Disorders

• Irritable bowel syndrome (IBS): Distinguished by pain that peaks before defecation, is relieved by defecation, and is associated with changes in stool form or frequency (Rome criteria) 1, 5, 6
• Microscopic colitis: Can cause secretory diarrhea without fever 5
• Inflammatory bowel disease (IBD): Should be considered, especially in travelers with persistent diarrhea 1

Malabsorption Syndromes

• Celiac disease: Can present with chronic diarrhea without fever 5
• Pancreatic exocrine insufficiency: Causes fatty diarrhea 5
• Bile acid malabsorption: Causes secretory diarrhea 5

Diagnostic Algorithm Based on Clinical Presentation

Acute Diarrhea (<14 days) Without Fever

If bloody stools present:

• Test for STEC (Shiga toxin detection and O157:H7 culture) as the primary concern 1, 2
• Consider Salmonella, Shigella, Campylobacter, though these typically present WITH fever 1
• Consider Entamoeba histolytica if travel history or persistent symptoms 1, 4

If watery, nonbloody stools:

• Viral gastroenteritis (norovirus) is most likely and requires no testing in uncomplicated cases 2
• Consider toxin-mediated bacterial illness if symptoms last <48 hours with prominent vomiting 1
• Test for Vibrio species if shellfish consumption or brackish water exposure 1

Persistent/Chronic Diarrhea (≥14 days) Without Fever

• Test for parasites: Giardia, Cryptosporidium, Cyclospora, Cystoisospora, Entamoeba histolytica 1
• Consider C. difficile if any antibiotic exposure in past 8-12 weeks 1, 2, 3
• Evaluate for non-infectious causes: IBS, IBD, celiac disease, microscopic colitis, medication effects 1, 5, 6

Critical Testing Indications

Stool testing is indicated even without fever if:

• Bloody or mucoid stools present 1, 2
• Severe abdominal cramping or tenderness 1, 2
• Immunocompromised status 1
• Recent hospitalization 2
• Persistent diarrhea >7-14 days 1, 2
• Outbreak setting (multiple people with similar symptoms) 1

Red Flags Requiring Urgent Evaluation

• Bloody diarrhea with anemia, thrombocytopenia, or renal dysfunction: Suspect hemolytic uremic syndrome (HUS) from STEC 2, 3
• Unintentional weight loss with bloody stools: Consider colorectal cancer 2, 5
• Severe dehydration or hemodynamic instability 3
• Signs of toxic megacolon or peritonitis 3

Critical Pitfalls to Avoid

• Do NOT give empiric antibiotics in immunocompetent patients with bloody diarrhea while awaiting test results, as this increases HUS risk in STEC infections 4, 2, 3
• Never use antibiotics for STEC O157 or Shiga toxin 2-producing STEC due to increased HUS risk 4, 2, 3
• Do not miss C. difficile testing in patients with recent antibiotic exposure, even without fever 1, 2, 3
• Consider immunocompromised status: These patients require broad differential including opportunistic pathogens (Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, CMV) even without fever 1