Discordant Fecal Biomarkers: Lactoferrin Elevation with Normal Calprotectin
Yes, lactoferrin can be elevated in stool while calprotectin levels remain normal, which creates diagnostic uncertainty that typically warrants further investigation. 1
Diagnostic Performance of Fecal Biomarkers
- Fecal lactoferrin has a sensitivity of 83% (95% CI, 72%-90%) and specificity of 75% (95% CI, 59%-87%) for detecting moderate to severe endoscopic inflammation in inflammatory bowel disease (IBD) 2
- Fecal calprotectin at a cutoff of 150 ± 50 mg/g has a sensitivity of 71% (95% CI, 62%-78%) and specificity of 69% (95% CI, 62%-75%) for detecting moderate to severe endoscopic inflammation 2
- Despite similar overall diagnostic accuracy (80-100% for both markers), these biomarkers can show discordant results in approximately 10% of cases 3, 4
Clinical Significance of Discordant Results
- Discordance between normal calprotectin and elevated lactoferrin may reflect segmental disease that might be missed by calprotectin alone 1
- Different clinical specialties use these markers differently - gastroenterologists tend to order calprotectin more frequently for abdominal pain, while primary care providers often order lactoferrin in the context of acute diarrhea 5
- The proportion of calprotectin orders has increased from 60% to nearly 90% compared to lactoferrin over the past decade, though the tests are not treated as equivalent by clinicians 5
Management Recommendations for Discordant Results
- For patients with normal calprotectin but elevated lactoferrin and mild symptoms, endoscopic assessment is recommended rather than empiric treatment adjustment 1
- For asymptomatic patients with this discordant pattern, repeat biomarker measurement in 3-6 months is suggested before proceeding to endoscopy 1
- If endoscopy confirms inflammation despite normal calprotectin, treatment should be adjusted based on endoscopic findings, and both biomarkers should continue to be monitored to establish which correlates better with the patient's disease activity 1
Potential Causes of Discordant Results
- Ileal Crohn's disease may show poor correlation between fecal markers and ileal inflammation - studies have shown that ileal endoscopic scores and histological findings failed to correlate with fecal markers 6
- Non-IBD conditions like Clostridium difficile infection can elevate both markers but with significant inter-individual variability 7
- Medications, particularly NSAIDs used in the past 6 weeks, can affect biomarker levels and should be considered when interpreting discordant results 1
- Different collection and processing methods can affect stability and measurement of these biomarkers 8
Practical Approach to Discordant Results
- Rule out infections first, particularly C. difficile and other enteric pathogens, as these can cause elevated inflammatory markers 2
- For patients with moderate to severe symptoms and elevated lactoferrin (even with normal calprotectin), consider treatment adjustment without routine endoscopic assessment 2
- For patients with mild symptoms and discordant markers, proceed with endoscopic assessment to confirm the presence or absence of inflammation 2, 1
- If endoscopy shows no inflammation despite elevated lactoferrin, consider other causes such as infections or medications, and repeat lactoferrin testing in 3-6 months 1