What is the role of fecal calprotectin testing in diagnosing and managing inflammatory bowel disease?

Fecal Calprotectin in Inflammatory Bowel Disease

Primary Diagnostic Role

Fecal calprotectin is a highly effective screening tool to differentiate inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) in patients aged 16-40 with chronic lower gastrointestinal symptoms, with excellent negative predictive value for ruling out IBD. 1

Diagnostic Thresholds and Actions

The British Society of Gastroenterology provides clear algorithmic guidance for primary care management 1:

• <100 μg/g: IBS is likely; treat as IBS in primary care 1
• 100-250 μg/g: Consider repeat testing or routine referral to gastroenterology (interpret based on pre-test probability) 1
• >250 μg/g: Refer urgently to gastroenterology 1

Higher thresholds (100-250 μg/g) are recommended to trigger colonoscopy, which improves positive predictive value with minimal reduction in negative predictive value. 2 A meta-analysis demonstrated that a cut-off of 50 μg/g had 90.6% sensitivity for detecting endoscopically active disease, while levels >100 μg/g provided 78.2% specificity. 2

Critical Pre-Test Considerations

Do not order fecal calprotectin if the patient has used NSAIDs in the past 6 weeks, as this invalidates the test. 1, 3 Other conditions that can cause false elevations include hemorrhoids (due to local bleeding and inflammation), infectious gastroenteritis, colorectal cancer, and liver cirrhosis. 2, 4

Disease Monitoring and Treatment Decisions

In Established IBD

Fecal calprotectin is a validated biomarker for endoscopic and histological disease activity that should guide treatment escalation or de-escalation decisions. 1

The American Gastroenterological Association provides specific guidance 2, 5:

• Asymptomatic patients in remission: Measure calprotectin every 6-12 months; levels <150 μg/g suggest minimal inflammation and predict sustained remission 2
• Moderate to severe symptoms with calprotectin >150 μg/g: This reliably indicates moderate to severe endoscopic inflammation (95.4% positive predictive value); adjust treatment empirically without requiring immediate endoscopy 2, 5
• Mild symptoms with calprotectin >150 μg/g: Perform endoscopic assessment rather than empiric treatment adjustment (15.5% false positive rate in this intermediate probability scenario) 5

Predicting Relapse

Clinically inactive disease with raised calprotectin levels predicts future relapse. 2 Serial monitoring at 3-6 month intervals facilitates early recognition and treatment of impending disease flares. 2, 5

Evidence for Biomarker-Guided Therapy

A randomized controlled trial demonstrated that treatment adjustment based on symptoms plus biomarkers (versus symptoms alone) increases the likelihood of achieving clinical and endoscopic remission at 12 months. 2

Practical Implementation

Sample Collection

Use the first stool passed in the morning and analyze within 3 days of collection at room temperature. 1, 3 This standardization minimizes variation related to stool transit time and degradation. 1

Interpretation Caveats

The test must be interpreted in clinical context 1:

• False negatives occur: A calprotectin <150 μg/g does not exclude inflammation in patients with moderate to severe symptoms (24.7% false negative rate) 5
• Celiac disease frequently causes false negatives (identified in multiple studies as a common cause of missed diagnoses) 4
• Not sensitive for colorectal cancer: Patients with alarm symptoms (rectal bleeding, abdominal pain, weight loss, iron deficiency anemia) require cancer pathway referral regardless of calprotectin result 2, 5

When Calprotectin is Unhelpful

Do not use fecal calprotectin to distinguish between IBD flare versus functional symptoms if the patient has concurrent conditions that elevate calprotectin (active hemorrhoids, recent NSAID use, acute infection). 1, 2 In these scenarios, proceed directly to endoscopic assessment if clinical suspicion for active IBD is high.

Superiority Over Other Biomarkers

Fecal calprotectin correlates more closely with endoscopic inflammation than serum CRP and provides direct evidence of intestinal mucosal inflammation rather than systemic inflammation. 6, 7 This makes it superior for detecting localized intestinal disease activity and for monitoring mucosal healing, which is the therapeutic target in modern IBD management. 8