Free White Blood Cells in Stool: Clinical Significance and Management
The presence of free white blood cells (fecal leukocytes) in stool suggests inflammatory diarrhea, but this test has poor diagnostic performance and should not be used to guide clinical decisions or antibiotic therapy. 1, 2
Why Fecal Leukocyte Testing Is Unreliable
The 2017 Infectious Diseases Society of America guidelines explicitly state that fecal leukocyte examination performs poorly for establishing infectious causes of diarrhea, particularly in hospitalized patients. 1, 2 The test has multiple technical and clinical limitations:
- Morphology degrades rapidly during specimen transport and processing, making accurate recognition and quantitation difficult 1, 2
- Intermittent presence and uneven distribution in stool significantly limits sensitivity 1, 2
- Poor specificity because fecal leukocytes appear in both infectious and non-infectious inflammatory conditions, including inflammatory bowel disease 1, 2
What Fecal Leukocytes Actually Indicate
When present, fecal leukocytes suggest inflammatory diarrhea, which may be caused by:
- Invasive bacterial pathogens such as Shigella, Salmonella, and Campylobacter 1
- Inflammatory bowel disease (ulcerative colitis or Crohn's disease) 1, 2
- Immune checkpoint inhibitor-associated colitis 1
- Other inflammatory conditions including ischemic colitis, diverticulitis, or drug-induced colitis 3, 4
The presence of both white blood cells and red blood cells together has modest predictive value for shigellosis specifically (positive predictive value 70-85%), but this varies by pathogen. 5, 6
Recommended Alternative Testing
Instead of relying on fecal leukocytes, use more reliable markers and definitive microbiologic testing:
- Stool lactoferrin or calprotectin are superior alternatives for differentiating inflammatory from non-inflammatory diarrhea because they remain stable during transport and processing 1, 2
- Stool culture for bacterial pathogens 1, 2
- C. difficile testing for nosocomial or antibiotic-associated diarrhea 1
- Molecular pathogen panels when available for comprehensive pathogen detection 2
Important caveat: Lactoferrin is a normal component of breast milk, making interpretation unreliable in breast-fed infants. 1, 2
Clinical Management Algorithm
When to pursue diagnostic workup for diarrhea:
Evaluate fecal specimens when diarrhea is accompanied by: 1
- Duration ≥1 day with fever, bloody stools, or systemic illness
- Recent antibiotic use
- Day-care center attendance
- Hospitalization
- Signs of dehydration (dry mucous membranes, decreased urination, tachycardia, orthostatic hypotension, lethargy)
For immune checkpoint inhibitor-associated diarrhea:
- Rule out infectious etiology first with stool culture, C. difficile testing, and CMV PCR 1
- Use inflammatory markers (fecal calprotectin preferred over leukocytes) and fecal occult blood testing 1
- Consider colonoscopy for grade ≥2 diarrhea after excluding infection, as ulceration on endoscopy predicts steroid-refractory disease 1
Do not use fecal leukocytes to:
- Guide antibiotic therapy decisions 2
- Distinguish between bacterial, viral, or parasitic causes 2
- Determine need for empirical treatment 1
Key Clinical Pitfall
The most common error is over-interpreting the presence or absence of fecal leukocytes to make treatment decisions. The test's poor sensitivity means their absence does not rule out inflammatory or bacterial diarrhea, and their presence does not confirm it. 1, 2 Always obtain definitive microbiologic testing rather than relying on this outdated screening test.