Management of Discordant Biomarkers in Inflammatory Bowel Disease

Understanding the Significance of Discordant Biomarkers

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 3

For patients with normal calprotectin but slightly elevated lactoferrin levels and mild symptoms, the American Gastroenterological Association recommends proceeding with endoscopic assessment rather than empiric treatment adjustment, as normal calprotectin with elevated lactoferrin creates diagnostic uncertainty that warrants direct visualization 1, 2, 5
For asymptomatic patients with normal calprotectin but elevated lactoferrin, the American Gastroenterological Association suggests repeating biomarker measurement in 3-6 months rather than immediate endoscopy, and proceeding with endoscopic assessment if lactoferrin remains elevated on repeat testing 2, 4

NSAID use in the past 6 weeks can affect biomarker levels and should be considered when interpreting results, with a strength of evidence level of moderate 6
The discordance between normal calprotectin and elevated lactoferrin may reflect potential segmental disease that might be missed by calprotectin alone, with a strength of evidence level of low 7

If endoscopy confirms active inflammation despite normal calprotectin, treatment should be adjusted based on endoscopic findings, and both biomarkers should be continued to be monitored to establish which one correlates better with the patient's disease activity, with a strength of evidence level of high 1, 7
If endoscopy shows no inflammation despite elevated lactoferrin, other causes of elevated lactoferrin such as infections or medications should be considered, and lactoferrin testing should be repeated in 3-6 months to confirm normalization, with a strength of evidence level of moderate 2, 6