What is the interpretation and management of an elevated calprotectin (fecal calprotectin) level?

Interpretation and Management of Elevated Fecal Calprotectin

Fecal calprotectin levels above 250 μg/g strongly suggest active intestinal inflammation requiring endoscopic assessment, while levels below 50 μg/g effectively rule out inflammatory bowel disease in most clinical scenarios. 1

Diagnostic Value of Fecal Calprotectin

Interpretation of Different Cutoff Values

• **<50 μg/g**: Normal range - high negative predictive value for IBD (>90%)

  • Only 1.4% of patients with this level will have endoscopic recurrence in low-risk scenarios 1
  • Effectively rules out active inflammation in most cases

• 50-100 μg/g: Borderline - may warrant repeat testing

  • Sensitivity of 88% but specificity only 67% for detecting active inflammation 1

• 100-250 μg/g: Moderate elevation

  • Suggests possible inflammation but has higher false positive rates
  • Specificity improves to 72% at 150 μg/g cutoff 1

• >250 μg/g: High elevation

  • Strong indication of active intestinal inflammation
  • Specificity of 74-79% for detecting active inflammation 1
  • Warrants prompt endoscopic assessment

Clinical Context Considerations

• Age: Higher baseline levels in children and elderly patients
• Symptoms: Bloody diarrhea requires endoscopic assessment regardless of calprotectin level 1
• Recent infection: Calprotectin remains elevated for weeks after infectious gastroenteritis 2
• Medication use: NSAIDs can cause elevated levels due to enteropathy 3

Management Algorithm Based on Calprotectin Level

For Patients Without Known IBD

1. <50 μg/g:

   • Low likelihood of IBD
   • Consider functional disorders (IBS) or non-inflammatory conditions
   • No endoscopic evaluation needed unless red flag symptoms present

2. 50-100 μg/g:

   • Consider repeat testing in 2-4 weeks
   • If persistent elevation, consider endoscopic assessment
   • Rule out infections and medication effects (NSAIDs)

3. 100-250 μg/g:

   • Endoscopic assessment recommended
   • Higher likelihood of IBD or other inflammatory conditions
   • Rule out infections with stool cultures/PCR before assuming IBD 4

4. >250 μg/g:

   • Prompt endoscopic assessment strongly recommended
   • High likelihood of active inflammation
   • Consider both IBD and non-IBD causes (infection, malignancy, NSAID enteropathy)

For Patients With Known IBD

1. <50 μg/g:

   • Suggests mucosal healing
   • Continue current therapy
   • Monitor periodically (every 3-6 months)

2. 50-150 μg/g:

   • Mild inflammation possible
   • Consider repeat testing in 4-8 weeks
   • If persistent, consider endoscopic assessment

3. >150 μg/g:

   • Suggests active inflammation despite clinical remission
   • Endoscopic assessment recommended before treatment adjustment 1
   • Rule out concurrent infection (occurs at similar rates as non-IBD patients) 4

4. >250 μg/g with symptoms:

   • High likelihood of active disease
   • Treatment intensification often warranted
   • Consider endoscopic confirmation based on clinical context

Special Considerations

Post-Surgical Monitoring in IBD

• Calprotectin <150 μg/g has good negative predictive value for endoscopic recurrence 1
• Consider endoscopic assessment 6-12 months after surgery regardless of calprotectin level

Differentiating IBD from IBS

• Calprotectin is cost-effective in identifying patients who need endoscopy 5
• Most cost-effective when pre-test probability of IBD is ≤75% in adults and ≤65% in children

Potential Pitfalls

• False positives: Infections, NSAID use, colorectal cancer, diverticulitis
• Day-to-day variability: Consider repeat testing for borderline results
• Different assays: Results may vary between laboratories and assay types 6
• Bacterial infections: Particularly Salmonella and Campylobacter can cause very high calprotectin levels (>600 μg/g) 2

Red Flags Requiring Endoscopy Regardless of Calprotectin

• Rectal bleeding with abdominal pain
• Change in bowel habits with weight loss
• Iron deficiency anemia
• Age >50 years with new GI symptoms 1

Fecal calprotectin is a valuable non-invasive biomarker for intestinal inflammation, but its interpretation must always consider the clinical context, and management decisions should be guided by both calprotectin levels and patient symptoms.