What is the clinical significance of elevated focal lactoferrin (lactoferrin) levels?

From the Guidelines

Elevated focal lactoferrin in stool samples is clinically significant as it indicates active intestinal inflammation, particularly in inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis. When lactoferrin levels are elevated in a focal area, this suggests localized inflammation rather than generalized intestinal inflammation. This finding helps differentiate IBD from non-inflammatory conditions such as irritable bowel syndrome (IBS), which typically shows normal lactoferrin levels. The presence of elevated focal lactoferrin should prompt further diagnostic evaluation, including colonoscopy with biopsies of the affected areas, imaging studies like CT enterography or MRI enterography, and other inflammatory markers such as calprotectin and CRP, as suggested by the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis 1. Management depends on the underlying cause but may include anti-inflammatory medications. According to the guideline, in patients with UC in symptomatic remission but elevated stool or serum markers of inflammation (fecal calprotectin >150 mg/g, elevated fecal lactoferrin, elevated CRP), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment 1. The diagnostic performance of fecal lactoferrin was reported in a study, with a sensitivity and specificity of 83% and 75%, respectively, for detecting endoscopic inflammation at a cutoff of 7.25 mg/g 2. Key points to consider in the management of patients with elevated focal lactoferrin include:

• The use of biomarkers such as fecal lactoferrin to monitor treatment response and adjust management accordingly
• The importance of considering the downstream consequences of testing and associated costs
• The need for individualized decision-making, taking into account patient preferences and values.

From the Research

Clinical Significance of Elevated Focal Lactoferrin

• Elevated focal lactoferrin is a sensitive and specific marker of disease activity in patients with inflammatory bowel disease (IBD) 3
• Fecal lactoferrin (FL) levels correlate significantly with erythrocyte sedimentation rate (ESR), hematocrit, albumin, and platelet count, and can be used to detect patients with clinically active disease 3
• Elevated FL levels may identify patients at greater risk for the development of subsequent clinical flares 3
• FL levels can mirror drug-induced changes in inflammation in ulcerative colitis and Crohn disease, and can be used to assess loss of response to biologics 4
• Timely monitoring of FL levels can rapidly predict therapeutic response in IBD, enabling rapid assessment of treatment efficacy 4

Diagnostic and Monitoring Applications

• Fecal markers, including lactoferrin and calprotectin, have been found to be more accurate than serum markers in diagnosing IBD 5
• Elevated lactoferrin levels can differentiate inflammatory disease from functional bowel disorders, but may not be specific for IBD 5
• Fecal lactoferrin can be used as a non-invasive tool to monitor disease activity and predict endoscopic and clinical relapse in patients with IBD 5, 6
• Lactoferrin has anti-inflammatory and immune-modulating properties, and may play a role in maintaining intestine mucosal immune homeostasis 7

Therapeutic Implications

• Elevated focal lactoferrin levels may indicate a need for adjustment of treatment strategies in patients with IBD 4
• Lactoferrin-based therapeutic interventions may be developed to target intestine mucosal immune system dysfunction in IBD 7
• Further research is needed to fully understand the clinical significance of elevated focal lactoferrin and its potential applications in the diagnosis and management of IBD 3, 4, 5, 6, 7