What is the treatment approach for a patient with elevated calprotectin levels indicative of intestinal inflammation?

Treatment Approach for Elevated Calprotectin Levels

For patients with elevated calprotectin levels indicative of intestinal inflammation, endoscopic assessment is strongly recommended rather than empiric treatment adjustment to accurately determine the underlying cause and guide appropriate therapy. 1

Understanding Calprotectin as a Biomarker

Fecal calprotectin is a neutrophil-derived protein that serves as a surrogate marker for intestinal inflammation. Key characteristics include:

• Primarily derived from neutrophils in the intestinal mucosa
• Elevated in various inflammatory conditions of the gut
• Normal values typically <50 μg/g, with values >150 μg/g suggesting active inflammation
• Excellent negative predictive value for ruling out inflammatory bowel disease (IBD)

Assessment Algorithm Based on Clinical Presentation

1. Patients in Symptomatic Remission with Elevated Calprotectin

For patients with IBD in symptomatic remission but elevated biomarkers (fecal calprotectin >150 mg/g, CRP >5 mg/L):

• Primary approach: Endoscopic assessment of disease activity rather than empiric treatment adjustment 1
• Alternative approach: Repeat measurement of biomarkers in 3-6 months if endoscopy was recently performed
• Exception: If biomarkers persistently elevated after recent resolution of symptoms, treatment adjustment may be warranted without endoscopy

2. Patients with Active Symptoms and Elevated Calprotectin

For patients with moderate to severe symptoms and elevated calprotectin (>150 mg/g):

• For UC patients: Elevated calprotectin can rule in active inflammation and inform treatment adjustment without routine endoscopy 1
• For CD patients: Elevated calprotectin >150 mg/g can inform treatment adjustment and avoid routine endoscopic assessment 1
• Caution: Patients requiring significant treatment adjustments (starting/switching immunosuppressive therapies) may benefit from endoscopic confirmation

3. Patients with Mild Symptoms and Elevated Calprotectin

• Recommended approach: Endoscopic assessment rather than empiric treatment adjustment 1
• Exception: In patients who recently underwent treatment adjustment for moderate-severe flare and now have mild residual symptoms, elevated biomarkers may guide further treatment adjustments

4. Patients with Normal Calprotectin

• If symptomatic with normal calprotectin (<150 mg/g), endoscopic assessment is recommended to rule out non-inflammatory causes of symptoms 1
• Values <50 μg/g are more reassuring and may point toward non-IBD etiology for symptoms 1

Important Considerations and Pitfalls

1. Diagnostic limitations:

   • Calprotectin is not specific for IBD; elevated levels can occur in colorectal cancer, gastrointestinal infections, and NSAID-induced enteropathy 2, 3
   • Values between 50-250 μg/g may be challenging to interpret as mild elevation can occur with non-specific low-grade inflammation 1

2. Interpretation challenges:

   • Different commercial assays show marked differences in performance 4
   • Age, medication use, and day-to-day variation can affect results
   • Calprotectin may better reflect disease activity in ulcerative colitis than in Crohn's disease 3

3. Treatment implications:

   • For confirmed IBD with elevated calprotectin, treatment options include:
     • For induction: Infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks 5
     • For maintenance: Adalimumab 40 mg every other week after induction 6
   • Treatment should target normalization of inflammatory markers in addition to symptom control

4. Follow-up monitoring:

   • Serial calprotectin monitoring at 3-6 month intervals may facilitate early recognition of impending disease flares 1
   • After symptom resolution and biomarker normalization, endoscopic evaluation should be performed 6-12 months after treatment initiation or adjustment 1

When to Consider Alternative Diagnoses

Always consider alternative diagnoses when calprotectin is elevated, especially in patients without established IBD:

• Colorectal cancer (even in younger patients) 2
• Infectious enteritis/colitis
• NSAID-induced enteropathy
• Microscopic colitis
• Celiac disease

The case presented in the evidence 2 highlights the importance of not assuming IBD in all cases of elevated calprotectin, as a young patient with elevated calprotectin (986 μg/g) was ultimately diagnosed with colon cancer rather than IBD.