Why Check Stool for White Blood Cells?
Checking stool for white blood cells (WBCs) is a historical practice with significant limitations that has largely been replaced by more reliable markers like lactoferrin or calprotectin in modern clinical practice. 1
Primary Historical Purpose
Stool WBCs were traditionally examined to:
- Distinguish inflammatory from non-inflammatory diarrhea - The presence of fecal leukocytes suggests intestinal inflammation, theoretically helping differentiate bacterial causes (like Shigella, Salmonella, or Campylobacter) from viral or non-inflammatory etiologies 2, 1
- Guide empirical antibiotic decisions - Positive fecal leukocytes were thought to identify patients more likely to benefit from antibiotic therapy, though this approach is no longer recommended 1, 3
Critical Limitations That Undermine Clinical Utility
The Infectious Diseases Society of America explicitly states that fecal leukocyte examination performs poorly for establishing infectious causes of diarrhea, particularly in hospitalized patients 2, 1. Key problems include:
- Rapid degradation - Fecal leukocyte morphology degrades during transport and processing, making accurate recognition and quantitation extremely difficult 2, 1
- Poor sensitivity - In inflammatory diarrhea, fecal leukocytes are intermittently present and unevenly distributed in stool, significantly limiting detection 2, 1
- Poor specificity - Fecal WBCs appear in both infectious AND non-infectious conditions, including inflammatory bowel disease (IBD), making them unable to distinguish between these entities 2, 1, 4
- Variable performance by setting - In developed countries, fecal leukocytes showed moderate discriminatory power (area under curve 0.89), but in resource-poor countries, performance dropped substantially (area under curve 0.72) 3
Modern Guideline Recommendations
The Infectious Diseases Society of America advises against relying on fecal leukocytes alone to guide antibiotic therapy decisions 1. Instead:
- Use lactoferrin or calprotectin - These markers are more stable during transport and processing than fecal leukocytes 2, 1
- Obtain definitive microbiologic testing - Stool culture, C. difficile toxin testing, and molecular pathogen panels should be pursued rather than relying on fecal leukocyte results 2, 1
- Consider clinical context - In IBD patients presenting with acute symptoms, stool cultures (especially for C. difficile) are mandatory, as these patients are at increased risk for infectious complications 2
Special Populations Where Interpretation Is Problematic
- Breast-fed infants - Lactoferrin is a normal component of human milk, making interpretation of surrogate markers difficult in this population 2, 1
- IBD patients - Both lactoferrin and calprotectin are elevated in non-infectious IBD, reducing specificity for infectious inflammatory diarrhea 2, 1
- Immunosuppressed patients - The WBC response may be blunted, leading to false-negative results 2
When Inflammatory Markers Remain Useful
Despite limitations of fecal leukocytes specifically, markers of intestinal inflammation still have a role:
- Risk stratification - Fecal calprotectin can help identify IBD patients at higher risk for complicated disease requiring imaging or endoscopy 2
- Distinguishing IBD from irritable bowel syndrome - Fecal calprotectin with a cutoff of 30 μg/g showed 100% sensitivity for active Crohn's disease versus IBS 2
- Monitoring IBD disease activity - Calprotectin correlates with clinical and endoscopic disease activity, though this is distinct from acute infectious evaluation 2
Bottom Line for Clinical Practice
Do not order fecal leukocytes for infectious diarrhea workup - proceed directly to stool culture, C. difficile testing, or molecular panels 1. If you need to assess for inflammatory versus non-inflammatory diarrhea, use lactoferrin or calprotectin instead 1. The test persists in some laboratories primarily for historical reasons, not because of strong supporting evidence for its clinical utility 2, 1.