What does an elevated calprotectin level indicate, and how should it be managed?

Elevated Calprotectin: Indication and Management

An elevated fecal calprotectin level primarily indicates intestinal inflammation, most commonly associated with inflammatory bowel disease (IBD), and should be managed with endoscopic assessment when levels exceed 150 μg/g, especially in symptomatic patients. 1

Diagnostic Significance of Elevated Calprotectin

Interpretation of Different Cutoff Values

• <50 μg/g: Normal value - suggests absence of significant intestinal inflammation

  • High negative predictive value (88% sensitivity) for ruling out IBD 2
  • Useful for differentiating IBD from irritable bowel syndrome (IBS) 1

• 50-150 μg/g: Borderline elevation

  • May indicate mild inflammation
  • Sensitivity decreases to 81% at 150 μg/g cutoff 2

• >150 μg/g: Significant elevation

  • Strongly suggests active intestinal inflammation
  • In symptomatic patients, reliably indicates moderate to severe endoscopic inflammation 1

• >250 μg/g: High elevation

  • Higher specificity (74%) for detecting active inflammation 2
  • Lower sensitivity (76%) compared to lower cutoffs 2

Correlation with Disease Activity

• Fecal calprotectin correlates well with endoscopic indices of disease severity in both Crohn's disease and ulcerative colitis 1
• Serves as a surrogate marker for neutrophilic intestinal inflammation 3
• Higher levels generally indicate more severe inflammation 4

Management Algorithm for Elevated Calprotectin

1. Symptomatic Patients with Elevated Calprotectin (>150 μg/g)

• Proceed to endoscopic evaluation to confirm diagnosis and assess disease severity 1
• If IBD is confirmed:
  • Initiate appropriate anti-inflammatory treatment based on disease type and severity
  • Target normalization of calprotectin alongside symptom control 1
  • Monitor response with serial calprotectin measurements at 3-6 month intervals 1

2. Asymptomatic Patients with Elevated Calprotectin

• Endoscopic assessment is recommended to rule out subclinical inflammation 1
• For patients who prefer to avoid immediate endoscopy:
  • Repeat calprotectin measurement in 3-6 months 1
  • If persistently elevated, endoscopy should be strongly considered

3. Known IBD Patients with Elevated Calprotectin

• In patients with symptoms: Consider treatment adjustment 1
• In patients without symptoms but elevated biomarkers:
  • Primary approach is endoscopic assessment rather than empiric treatment adjustment 1
  • After symptom resolution and biomarker normalization, perform endoscopic evaluation 6-12 months after treatment initiation/adjustment 1

Important Considerations and Pitfalls

Differential Diagnosis of Elevated Calprotectin

• Not specific to IBD - can be elevated in:
  • Colorectal cancer 5
  • Gastrointestinal infections 4
  • NSAID-induced enteropathy 1
  • Liver cirrhosis 6
  • Other inflammatory conditions of the gut 1

Testing Considerations

• First morning stool sample is recommended 1
• Sample should be stored for no more than 3 days at room temperature 1
• Consider variability between different assays and day-to-day variation 1, 7

Common Pitfalls

• False negatives: Relying solely on normal calprotectin to exclude IBD in highly suspicious cases
• False positives: Initiating IBD treatment based solely on elevated calprotectin without endoscopic confirmation
• Overtreatment: The American Gastroenterological Association recommends against initiating empiric anti-inflammatory treatment based solely on symptoms when calprotectin is normal 1
• Misinterpretation: Not considering other causes of elevated calprotectin beyond IBD

Monitoring and Follow-up

• For confirmed IBD:
  • Serial monitoring at 3-6 month intervals 1
  • Target normalization of calprotectin as a treatment goal 1
  • Persistently elevated levels despite treatment may indicate inadequate therapy or development of complications

By following this structured approach to elevated calprotectin levels, clinicians can appropriately diagnose and manage intestinal inflammation while avoiding unnecessary treatments or missed diagnoses.