What is the significance of elevated calprotectin levels in stool?

Significance of Elevated Fecal Calprotectin Levels

Elevated fecal calprotectin (>150 μg/g) indicates active intestinal inflammation and should prompt further evaluation for inflammatory bowel disease (IBD) or other inflammatory conditions through endoscopic assessment. 1, 2

Understanding Fecal Calprotectin

Fecal calprotectin is a calcium- and zinc-binding protein primarily derived from neutrophils that serves as a biomarker for intestinal inflammation. It has emerged as a valuable non-invasive tool to differentiate between inflammatory and non-inflammatory gastrointestinal conditions.

Interpretation of Calprotectin Levels

Level	Interpretation	Action
<50 μg/g	Normal	IBS likely, manage in primary care [1]
50-150 μg/g	Borderline	Consider repeat testing or routine referral [1,2]
>150 μg/g	Elevated	Refer for endoscopic assessment [1]
>250 μg/g	Highly elevated	Urgent referral to gastroenterology [1,2]

Clinical Significance of Elevated Levels

Elevated fecal calprotectin has several important clinical implications:

• Differentiating IBD from IBS: Fecal calprotectin has high sensitivity (90.6%) for detecting endoscopically active disease at a cut-off of 50 μg/g and best specificity (78.2%) at levels >100 μg/g 1

• Disease activity monitoring: In patients with known IBD, elevated levels correlate well with endoscopic inflammation in both ulcerative colitis and Crohn's disease 1

• Predicting relapse: In patients with IBD in symptomatic remission but elevated biomarkers, repeat measurement in 3-6 months is recommended 1, 2

• Treatment decisions: The American Gastroenterological Association (AGA) suggests using fecal calprotectin >150 mg/g to rule in active inflammation and inform treatment adjustments in patients with moderate to severe symptoms 1

Management Algorithm Based on Calprotectin Levels

For New Patients with GI Symptoms (Age 16-40):

1. If calprotectin <100 μg/g:

   • IBS likely
   • Treat as IBS in primary care
   • Consider other differential diagnoses if symptoms persist 1

2. If calprotectin 100-250 μg/g:

   • Consider repeat testing
   • Consider routine referral to gastroenterology 1

3. If calprotectin >250 μg/g:

   • Refer urgently to gastroenterology
   • Exclude infectious causes before further investigation 1

For Known IBD Patients:

1. If symptomatic with elevated calprotectin (>150 μg/g):

   • In moderate to severe symptoms: Use to confirm active inflammation and adjust treatment without routine endoscopy 1
   • In mild symptoms: Endoscopic assessment recommended before treatment adjustment 1

2. If asymptomatic with elevated calprotectin:

   • Repeat measurement in 3-6 months
   • If persistently elevated, endoscopic assessment warranted 1, 2

Important Caveats and Pitfalls

• False positives: Calprotectin may be elevated in:

  • Non-intestinal infections or inflammation
  • Colorectal cancer
  • Infectious gastroenteritis
  • NSAID use
  • Recent colonoscopy 1, 2

• Sample collection: First morning stool is recommended; samples should be stored for no more than 3 days at room temperature 1

• Age considerations: Calprotectin levels naturally increase with age 2

• Test variability: Different commercial assays may have varying thresholds and performance characteristics 2

• Not for cancer screening: Fecal calprotectin is not sensitive enough to exclude advanced colorectal adenoma or colorectal carcinoma 1

By understanding the significance of elevated fecal calprotectin and following appropriate management algorithms, clinicians can effectively utilize this biomarker to improve patient outcomes through early diagnosis, appropriate treatment, and monitoring of intestinal inflammatory conditions.