What does it mean to have positive lactoferrin and increased fecal calprotectin?

Positive Lactoferrin and Elevated Fecal Calprotectin: Clinical Significance

Both positive lactoferrin and elevated fecal calprotectin (>150 μg/g) indicate active intestinal inflammation, most commonly from inflammatory bowel disease (IBD), and your next steps depend critically on symptom severity. 1, 2

What These Results Mean

Both biomarkers are neutrophil-derived proteins released during intestinal inflammation, and when both are elevated together, they strongly suggest active inflammatory disease in your gastrointestinal tract 3:

• Fecal calprotectin >150 μg/g has 71% sensitivity and 69% specificity for detecting moderate to severe endoscopic inflammation 4
• Elevated fecal lactoferrin has 83% sensitivity and 75% specificity for detecting moderate to severe endoscopic inflammation 4
• When both are elevated simultaneously, this concordance (seen in 90% of cases) provides strong evidence of active inflammation 5

Clinical Algorithm Based on Symptom Severity

If You Have Moderate to Severe Symptoms

(Frequent rectal bleeding with bleeding score 2-3, significantly increased stool frequency)

You can adjust treatment empirically without requiring endoscopy first 1, 2:

• With both markers elevated and moderate-to-severe symptoms, the false positive rate is only 4.6%, meaning 95.4% of patients truly have moderate to severe endoscopic inflammation 2
• The AGA specifically recommends using fecal calprotectin >150 mg/g or elevated fecal lactoferrin to rule in active inflammation and inform treatment adjustment while avoiding endoscopic assessment solely for establishing disease presence 1
• Proceed with appropriate IBD therapy intensification based on disease type and severity 6

If You Have Mild Symptoms

(Infrequent rectal bleeding, mildly increased stool frequency)

You should undergo endoscopic assessment before making treatment changes 1, 4:

• With mild symptoms, elevated biomarkers have a 15.5% false positive rate for moderate-to-severe inflammation 2
• The AGA specifically recommends endoscopic assessment rather than empiric treatment adjustment in this scenario 1
• This approach prevents unnecessary treatment escalation in patients who may not have significant endoscopic disease 4

If You Are Asymptomatic

(Known IBD patient without current symptoms)

Proceed with endoscopic evaluation, as the false positive rate is 22.4% in asymptomatic patients 2:

• Elevated biomarkers in asymptomatic patients warrant investigation but are less reliable predictors of endoscopic inflammation 2
• Consider repeat biomarker measurement in 3-6 months if endoscopy is not immediately feasible 4

Important Caveats and Pitfalls

Rule Out Infections First

Always exclude C. difficile and other enteric pathogens before attributing elevated markers solely to IBD 4, 7:

• C. difficile infection significantly elevates both calprotectin (median 218 μg/g) and lactoferrin (median 26.8 μg/g) 7
• Patients with detectable C. difficile toxin in stools have even higher levels (calprotectin 274 μg/g, lactoferrin 39.2 μg/g) 7

Medication Effects

NSAIDs used within the past 6 weeks can elevate both biomarkers and should be considered when interpreting results 4

Other Causes of Elevation

Fecal calprotectin and lactoferrin are not specific for IBD alone 2:

• Colorectal neoplasia
• Gastrointestinal infections
• Celiac disease
• Medication effects (particularly NSAIDs)

Location-Specific Limitations

Both markers correlate poorly with isolated ileal disease 8:

• In pure ileal Crohn's disease, neither calprotectin (p=0.161) nor lactoferrin (p=0.448) correlates with ileal endoscopic scores 8
• Both markers correlate significantly with ileocolonic and colonic disease activity (p<0.001) 8

Monitoring After Treatment Initiation

Repeat fecal calprotectin measurement 2-4 months after initiating or adjusting therapy to monitor response 6:

• Both calprotectin and lactoferrin decline significantly with successful anti-TNF therapy (calprotectin from median 1173 to 130 μg/g, lactoferrin from 105 to 2.7 μg/g) 9
• Patients achieving endoscopic remission show dramatic declines (calprotectin from 1891 to 27 μg/g, lactoferrin from 92.4 to 1.9 μg/g) 9
• Consider endoscopic assessment 6-12 months after treatment initiation to confirm mucosal healing 6

Why Both Tests Were Ordered

Calprotectin and lactoferrin provide complementary information 3:

• Calprotectin correlates more strongly with endoscopic inflammation 3, 8
• Lactoferrin correlates more strongly with histological inflammation 3, 8
• Both tests together improve diagnostic accuracy, with overall diagnostic efficacy of 80% for calprotectin and 81% for lactoferrin 3