How to manage a suspected calprotectin (fecal calprotectin) false positive result in a patient?

Management of Suspected Fecal Calprotectin False Positive Results

When faced with a suspected false positive fecal calprotectin result, repeat testing after approximately 18 days is recommended as this can show reduction in calprotectin levels in up to 53% of patients with initially elevated results. 1

Common Causes of False Positive Results

• Non-steroidal anti-inflammatory drugs (NSAIDs) use within the past 6 weeks can cause false elevations in fecal calprotectin and should be discontinued before testing 2, 3
• Presence of hemorrhoids or other sources of gastrointestinal bleeding can elevate calprotectin levels without indicating inflammatory bowel disease 2
• Liver cirrhosis has been associated with false positive calprotectin results 3
• Infectious gastroenteritis will cause elevated calprotectin and cannot be distinguished from IBD by calprotectin alone 4
• Colorectal cancer and advanced adenomas can also cause elevated calprotectin levels 2

Diagnostic Approach for Suspected False Positives

Initial Assessment

• Review medication history, particularly focusing on recent NSAID use 3
• Evaluate for other potential causes of inflammation including infectious gastroenteritis through stool cultures 4
• Consider the clinical context - calprotectin is not recommended for patients with rectal bleeding, abdominal pain, change in bowel habit, weight loss, or iron-deficiency anemia where cancer pathway referral should be prioritized 1

Follow-up Testing

• For mildly elevated results (100-250 μg/g), repeat testing after approximately 18 days is recommended 1, 4
• For patients with elevated calprotectin but no symptoms, repeat measurement in 3-6 months is reasonable before proceeding to endoscopy 5
• If calprotectin remains elevated on repeat evaluation, endoscopic assessment is warranted 5

Interpretation of Results Based on Clinical Context

For Patients with Mild Symptoms (100-250 μg/g)

• The negative predictive value of a fecal calprotectin between 100-200 μg/g in excluding significant organic GI disease is high (97.5% for significant luminal pathology) 6
• In adult patients under 50 years with new lower GI symptoms and mildly elevated calprotectin (100-200 μg/g), only 2.5% were eventually diagnosed with IBD after long-term follow-up 6

For Patients with Moderate to Severe Symptoms

• Endoscopic assessment (flexible sigmoidoscopy or colonoscopy) is recommended rather than relying solely on calprotectin results 1
• Stool culture and/or flexible sigmoidoscopy or colonoscopy are the appropriate diagnostic investigations in acute presentations 4

Practical Considerations for Calprotectin Testing

• The first stool passed in the morning should be routinely used for sampling 1
• Samples should be stored for no more than 3 days at room temperature before analysis 1
• Variability exists between different calprotectin assays, and results should be interpreted according to local laboratory reference ranges 4
• Home fecal calprotectin testing can be a valid alternative when access to laboratory testing is limited 1

Clinical Algorithm for Managing Suspected False Positive Results

1. Verify pre-test conditions:

   • Confirm no NSAID use in the past 6 weeks 2
   • Ensure proper sample collection and storage 1

2. Evaluate clinical context:

   • If patient has alarm symptoms (rectal bleeding, weight loss, anemia), proceed directly to endoscopic evaluation regardless of calprotectin level 1
   • For patients with mild symptoms and calprotectin 100-250 μg/g, consider repeat testing 1, 4
   • For patients with moderate-severe symptoms, proceed to endoscopic evaluation 1

3. Repeat calprotectin testing:

   • If repeat test shows normalization (<100 μg/g), false positive is confirmed 1
   • If repeat test remains elevated but patient is asymptomatic, consider monitoring with repeat testing in 3-6 months 5
   • If repeat test remains elevated and patient is symptomatic, proceed to endoscopic evaluation 5

4. Endoscopic evaluation:

   • If endoscopy is normal, consider other causes of elevated calprotectin (NSAIDs, hemorrhoids, microscopic colitis) 2, 3
   • If endoscopy confirms inflammation, manage according to findings 1

By following this structured approach, clinicians can appropriately manage suspected false positive calprotectin results while minimizing unnecessary investigations and ensuring that significant pathology is not missed.