What are the next steps after a positive calprotectin test?

Management of a Positive Calprotectin Test

After a positive fecal calprotectin test, the next step should be endoscopic assessment to confirm the presence and extent of intestinal inflammation, particularly when the level exceeds 150 μg/g. 1

Interpreting Calprotectin Results

Fecal calprotectin is a sensitive and specific marker of intestinal inflammation that serves as a useful non-invasive method to investigate gastrointestinal symptoms. Results can be interpreted as follows:

• **<50 μg/g**: Normal range with high negative predictive value (>90%) for inflammatory bowel disease (IBD)
• 50-100 μg/g: Borderline, may warrant repeat testing
• 100-250 μg/g: Moderate elevation suggesting possible inflammation
• >250 μg/g: High elevation strongly indicating active intestinal inflammation, warranting prompt endoscopic assessment 1

Algorithm for Management Based on Calprotectin Level and Symptoms

1. Asymptomatic Patients with Elevated Calprotectin

• If calprotectin <150 μg/g: Consider repeat testing in 4-6 weeks
• If calprotectin >150 μg/g: Proceed to endoscopic assessment 1

2. Patients with Mild Symptoms and Elevated Calprotectin

• If calprotectin >150 μg/g: Endoscopic assessment is recommended rather than empiric treatment 1
• If calprotectin <150 μg/g: Endoscopic assessment is still suggested as a significant proportion of symptomatic patients with low calprotectin may have endoscopic activity 1

3. Patients with Moderate to Severe Symptoms

• If calprotectin >150 μg/g: Use calprotectin to rule in active inflammation and inform treatment adjustment without routine endoscopic assessment 1
• If calprotectin <150 μg/g: Endoscopic assessment is recommended rather than empiric treatment 1

4. Special Considerations

• Bloody diarrhea: Requires endoscopic assessment regardless of calprotectin level 1, 2
• Suspected colorectal cancer: Calprotectin is not sensitive enough to exclude advanced colorectal adenoma or colorectal carcinoma; standard cancer referral pathways should be followed 1
• Post-operative IBD patients: Calprotectin <150 μg/g has good negative predictive value for endoscopic recurrence 2

Differential Diagnosis to Consider

When evaluating elevated calprotectin, consider:

1. Inflammatory Bowel Disease (IBD): Crohn's disease or ulcerative colitis
2. Infectious gastroenteritis: Rule out with stool cultures
3. Colorectal neoplasia: Consider in appropriate age groups or with alarm symptoms
4. Microscopic colitis
5. NSAID-induced enteropathy: Can cause elevated calprotectin levels 2
6. Celiac disease
7. Diverticulitis

Important Caveats

• Disease location matters: Fecal calprotectin may be modestly less accurate in detecting inflammation in small bowel disease compared to colonic involvement 1
• Assay variability: Different calprotectin assays may not be interchangeable; use the same assay for a given patient to compare results over time 1
• Within-patient variation: Substantial within-stool and within-day variation can occur; repeat testing may be needed for borderline or unexpected results 1
• False positives: Several conditions other than IBD can increase fecal calprotectin, including colorectal neoplasia and gastrointestinal infections 3
• Medication effects: NSAIDs and proton pump inhibitors can cause elevated calprotectin levels 2

When to Refer to a Specialist

Prompt referral to a gastroenterologist is indicated when:

• Calprotectin >250 μg/g
• Persistent elevation >150 μg/g on repeat testing
• Presence of alarm symptoms (rectal bleeding, weight loss, anemia)
• Moderate to severe symptoms despite normal calprotectin 1

Remember that while fecal calprotectin is a valuable tool for detecting intestinal inflammation, endoscopic assessment remains the gold standard for diagnosing IBD and evaluating disease extent and severity.