What is the difference between stool calprotectin and fecal leukocytes (white blood cells) in diagnosing gastrointestinal symptoms?

Stool Calprotectin vs Fecal Leukocytes: Key Differences

Fecal calprotectin has replaced fecal leukocytes as the preferred biomarker for detecting intestinal inflammation because it is more stable, quantifiable, and has superior diagnostic accuracy. 1

Why Calprotectin is Superior

Stability and Practicality

• Calprotectin remains stable in stool for up to 3 days at room temperature, making it practical for outpatient collection and transport 2, 3
• Fecal leukocytes degrade rapidly after stool passage, requiring immediate microscopic examination and limiting clinical utility
• The first morning stool sample is recommended for calprotectin testing 2, 3

Quantifiable and Standardized

• Calprotectin provides objective numerical values (μg/g) with established clinical thresholds, enabling consistent interpretation across laboratories 1
• Fecal leukocytes rely on subjective microscopic assessment (present/absent or semi-quantitative grading), leading to poor inter-observer reliability
• Standard cutoffs for calprotectin: <50 μg/g suggests no inflammation, 50-250 μg/g is indeterminate, >250 μg/g indicates active inflammation 1

Diagnostic Performance

• Calprotectin at 50 μg/g cutoff has 90.6% sensitivity for detecting endoscopically active IBD 2
• At 150 μg/g cutoff, calprotectin demonstrates 71% sensitivity and 69% specificity for moderate-to-severe endoscopic inflammation in ulcerative colitis 1
• Calprotectin has excellent negative predictive value (>95%) for ruling out IBD, making it ideal for avoiding unnecessary colonoscopies 4, 5

Clinical Applications Where Calprotectin Excels

Differentiating IBD from IBS

• Calprotectin <50 μg/g effectively rules out IBD in patients with chronic diarrhea, with only 1% developing IBD over 12 months 1
• This allows confident diagnosis of IBS without endoscopy in appropriate clinical contexts 5, 6

Distinguishing Bacterial from Viral Gastroenteritis

• Calprotectin is significantly elevated in bacterial gastroenteritis (median 765-1870 μg/g) compared to viral gastroenteritis (median 89-95 μg/g) 7, 8
• At 710 μg/g cutoff, calprotectin has 88.9% sensitivity and 76.0% specificity for bacterial gastroenteritis 7
• Fecal leukocytes show similar patterns but lack quantitative precision

Monitoring IBD Activity

• In symptomatic remission, calprotectin <150 μg/g reliably excludes active inflammation, avoiding unnecessary endoscopy 1, 2
• Elevated calprotectin (>150 μg/g) in asymptomatic IBD patients predicts future relapse 2, 9
• Serial monitoring every 3-6 months facilitates early detection of disease flares 2, 9

Important Caveats

Non-Specific Elevations

Both calprotectin and fecal leukocytes can be elevated by:

• NSAIDs (within past 6 weeks) 2, 3
• Colorectal cancer 1
• Infectious gastroenteritis 1, 7
• Hemorrhoids (can cause false elevations) 2

Limitations

• Calprotectin is not sensitive enough to exclude colorectal cancer or advanced adenomas 2
• Patients with alarm symptoms (rectal bleeding, weight loss) require endoscopy regardless of calprotectin level 9
• Indeterminate values (50-250 μg/g) carry 8% risk of IBD and may require repeat testing or endoscopy 1

Guideline-Based Recommendations

Primary Care Screening

• Initial workup for chronic diarrhea should include fecal calprotectin (not fecal leukocytes) along with CBC, ferritin, tissue transglutaminase, and thyroid function 1

Referral Thresholds

• Calprotectin <100 μg/g: IBS likely, no referral needed 2
• Calprotectin 100-250 μg/g: Consider repeat testing or routine gastroenterology referral 2
• Calprotectin >250 μg/g: Urgent gastroenterology referral indicated 2, 9

IBD Management

• In patients with moderate-to-severe IBD symptoms and calprotectin >150 μg/g, empiric treatment escalation is appropriate without endoscopy 1, 9
• In patients with mild symptoms and calprotectin >150 μg/g, endoscopic assessment is preferred before treatment changes 1, 9