What is the management approach for a patient with normal calprotectin but slightly elevated lactoferrin levels?

Management Approach for a Patient with Normal Calprotectin but Slightly Elevated Lactoferrin

Endoscopic assessment is recommended for patients with normal calprotectin but slightly elevated lactoferrin levels, rather than empiric treatment adjustment, especially in patients with mild symptoms. 1

Understanding the Significance of Discordant Biomarkers

• Fecal calprotectin and lactoferrin are both neutrophil-derived markers that correlate with intestinal inflammation, but they may not always show concordance in their results 2, 3
• While calprotectin is the more commonly used marker (increasing from 60% to 90% of orders over the past decade), lactoferrin has similar sensitivity and specificity for detecting inflammation 4
• The sensitivity and specificity of fecal lactoferrin for detecting moderate to severe endoscopic inflammation is 83% and 75% respectively, making it a reliable marker for inflammation 1

Recommended Management Algorithm

For Asymptomatic Patients:

• If the patient is in symptomatic remission (no rectal bleeding, normal stool frequency) with normal calprotectin but elevated lactoferrin:
  • Repeat biomarker measurement in 3-6 months rather than immediate endoscopy 1
  • If lactoferrin remains elevated on repeat testing, proceed with endoscopic assessment 1

For Patients with Mild Symptoms:

• If the patient has mild symptoms (infrequent rectal bleeding and/or slightly increased stool frequency):
  • Proceed with endoscopic assessment rather than empiric treatment adjustment 1
  • This is particularly important as normal calprotectin with elevated lactoferrin creates diagnostic uncertainty that warrants direct visualization 1

For Patients Recently Treated for Flare:

• If the patient recently underwent treatment adjustment for moderate to severe symptoms and now has mild residual symptoms:
  • The elevated lactoferrin may be used to inform treatment adjustments (such as dose optimization) 1
  • Consider the timing of testing in relation to recent therapy changes 1

Clinical Considerations and Caveats

• Biomarkers are not specific for IBD and may be elevated in other organic conditions 5
• NSAID use in the past 6 weeks can affect biomarker levels and should be considered when interpreting results 6
• Lactoferrin correlates particularly well with histological inflammation, while calprotectin may better reflect endoscopic findings 3
• The discordance between normal calprotectin and elevated lactoferrin may reflect:
  • Different aspects of the inflammatory process 2
  • Potential segmental disease that might be missed by calprotectin alone 7
  • Possible early relapse that is not yet detectable by calprotectin 8

Monitoring Recommendations

• If endoscopy confirms active inflammation despite normal calprotectin:
  • Adjust treatment based on endoscopic findings 1
  • Continue monitoring with both biomarkers to establish which one correlates better with this specific patient's disease activity 7
• If endoscopy shows no inflammation despite elevated lactoferrin:
  • Consider other causes of elevated lactoferrin (infections, medications) 6
  • Repeat lactoferrin testing in 3-6 months to confirm normalization 1

Remember that while biomarkers are valuable tools for monitoring inflammatory bowel disease, they should be interpreted in the clinical context, and endoscopy remains the gold standard for assessing mucosal inflammation 2.