What does a high stool calprotectin level indicate and how is it treated?

High Stool Calprotectin: Clinical Significance and Management

Elevated fecal calprotectin indicates intestinal inflammation, most commonly from inflammatory bowel disease (IBD), and requires further evaluation with endoscopy for diagnosis and treatment planning rather than empiric therapy alone. 1, 2

What Elevated Calprotectin Indicates

Interpretation by Level

• <50 μg/g: Normal range; IBD is unlikely with high negative predictive value (99%), making it excellent for ruling out inflammatory disease 3, 1

• 50-100 μg/g: Low-level elevation; IBD remains unlikely, though an 8% chance of developing IBD within 12 months exists compared to 1% in those with normal levels 3

• 100-250 μg/g: Intermediate range requiring clinical correlation; warrants either repeat testing in 2-3 weeks or gastroenterology referral depending on symptom severity 1

• >150 μg/g: Strongly suggests active intestinal inflammation, particularly in patients with moderate-to-severe symptoms, with 95.4% having confirmed endoscopic inflammation 1, 2

• >250 μg/g: Indicates significant active inflammation correlating well with endoscopic disease activity and typically requires urgent gastroenterology referral 3, 1

Conditions Associated with Elevation

Calprotectin is not specific to IBD and can be elevated in multiple conditions 3, 1:

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) - most common cause
• Colorectal cancer - though not sensitive enough to exclude malignancy
• Infectious gastroenteritis - acute bacterial or parasitic infections
• NSAID use within the past 6 weeks
• Microscopic colitis
• Hemorrhoids - can cause false elevation due to local bleeding and inflammation 1

How to Manage Elevated Calprotectin

Initial Diagnostic Workup

Complete baseline testing before or concurrent with gastroenterology referral 1:

• Stool culture to exclude infectious causes 1
• Complete blood count to assess for anemia and thrombocytosis indicating inflammation 1
• C-reactive protein as complementary inflammatory marker (though 20% of active Crohn's patients have normal CRP) 1
• Celiac screen (tissue transglutaminase antibodies) to exclude celiac disease 1
• Urea and electrolytes to assess for dehydration and electrolyte abnormalities 1

Management Algorithm Based on Clinical Presentation

Patients with Moderate-to-Severe Symptoms + Calprotectin >150 μg/g

In patients with moderate-to-severe symptoms (rectal bleeding, significant abdominal pain, weight loss, frequent diarrhea) and calprotectin >150 μg/g, treatment can be adjusted empirically without routine endoscopic assessment, as this combination reliably indicates moderate-to-severe endoscopic inflammation. 1, 2

• The false positive rate is only 4.6% in this scenario 2
• Urgent gastroenterology referral is still recommended for treatment planning 1

Patients with Mild Symptoms + Calprotectin >150 μg/g

Endoscopic assessment is required before treatment adjustment in patients with mild symptoms and elevated calprotectin >150 μg/g, as the false positive rate is 15.5% in this intermediate probability scenario. 1, 2

Patients with Intermediate Levels (100-250 μg/g)

Consider repeat calprotectin testing after 2-3 weeks if symptoms are mild, as 53% of patients show reduction on repeat testing. 1, 4

• If repeat testing shows <100 μg/g and symptoms suggest IBS, manage as IBS in primary care 1
• If persistently elevated or symptoms worsen, proceed to gastroenterology referral 1

Asymptomatic Patients with Known IBD + Calprotectin >150 μg/g

Endoscopic assessment should be considered, as elevated calprotectin in clinically inactive disease predicts future relapse. 1

• The false positive rate is 22.4% in asymptomatic patients 2
• Serial monitoring at 3-6 month intervals can facilitate early recognition of impending flares 1, 2

Definitive Diagnosis Requires Endoscopy

Ileocolonoscopy with biopsies remains the gold standard for diagnosing IBD, assessing disease extent and severity, and differentiating Crohn's disease from ulcerative colitis. 1

• Cross-sectional imaging (MRI or CT enterography) may be needed to assess small bowel involvement and complications 1

Critical Caveats and Pitfalls

When Calprotectin Should NOT Guide Management

If alarm features are present (rectal bleeding with abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia), referral via suspected cancer pathway is required regardless of calprotectin level, as calprotectin is not sensitive enough to exclude colorectal cancer. 1, 4

Acute Diarrhea Settings

In acute diarrhea, calprotectin will not discriminate between IBD and gastroenteritis; stool culture and/or flexible sigmoidoscopy are the appropriate diagnostic investigations. 4

• For bloody diarrhea, flexible sigmoidoscopy is indicated regardless of calprotectin result 4

NSAID Confounding

NSAID use within the past 6 weeks can falsely elevate calprotectin; repeat testing after NSAID cessation is appropriate if recent use is documented. 1

False Negatives

In patients with moderate-to-severe symptoms, calprotectin <150 μg/g does not exclude inflammation, with a false negative rate of 24.7%. 2

• Clinical judgment and endoscopic evaluation remain essential when suspicion is high 2

Monitoring Treatment Response in Established IBD

In patients with known IBD in symptomatic remission, measure calprotectin every 6-12 months to detect subclinical inflammation and predict relapse. 1

• Calprotectin <50 μg/g is generally reassuring and suggests clinical remission 2
• Elevated calprotectin in clinically quiescent disease predicts relapse within 12 months 1, 5
• Treatment adjustment based on symptoms plus biomarkers (versus symptoms alone) increases the likelihood of achieving clinical and endoscopic remission at 12 months 1