What are the next steps in managing a patient with elevated fecal calprotectin levels?

Management of Elevated Fecal Calprotectin

In patients with elevated fecal calprotectin >150 μg/g, the next management step depends critically on symptom severity: proceed directly to treatment adjustment in moderate-to-severe symptoms, but perform endoscopic assessment before treatment changes in mild or absent symptoms. 1

Clinical Context Assessment

First, determine the clinical scenario by evaluating:

• Symptom severity: Classify as asymptomatic/remission, mild symptoms (slight increase in stool frequency, infrequent rectal bleeding), or moderate-to-severe symptoms (significant diarrhea, frequent bleeding, abdominal pain) 1
• Known IBD vs. new diagnosis: Management algorithms differ substantially 1
• Medication history: NSAIDs, aspirin, and PPIs can elevate calprotectin and confound interpretation 2
• Infection exclusion: Test for Clostridioides difficile and other enteric pathogens, as these elevate biomarkers independent of IBD activity 1

Management Algorithm by Clinical Scenario

Moderate-to-Severe Symptoms + Calprotectin >150 μg/g

Proceed with empiric treatment adjustment without routine endoscopy. 1

• The false positive rate is only 4.6% in this high pretest probability scenario, meaning 95.4% of these patients have true endoscopic inflammation 3
• For ulcerative colitis: Adjust or intensify current therapy based on disease severity 1
• For Crohn's disease: Treatment adjustment is appropriate given the high likelihood of active inflammation 1
• Exception: Patients who place high value on confirming inflammation before major treatment decisions (e.g., starting biologics) may reasonably choose endoscopy first 1

Mild Symptoms + Calprotectin >150 μg/g

Perform endoscopic assessment before treatment adjustment. 1

• The false positive rate increases to 15.5% in this intermediate pretest probability scenario 3
• Direct endoscopy may be more efficient than biomarker testing in patients with mild symptoms 1
• Alternative approach: In patients who underwent recent treatment adjustment with residual mild symptoms, elevated biomarkers may inform dose adjustments without endoscopy 1

Asymptomatic/Symptomatic Remission + Calprotectin >150 μg/g

Perform endoscopic assessment rather than empiric treatment. 1

• The false positive rate is 22.4% in asymptomatic patients, making empiric treatment inappropriate 3
• Reasonable alternative: Repeat calprotectin measurement in 3-6 months; if persistently elevated, then proceed to endoscopy 1
• This approach balances avoiding unnecessary procedures while not missing subclinical inflammation

Mild Symptoms + Calprotectin <150 μg/g

Perform endoscopic assessment rather than empiric treatment or reassurance alone. 1

• Normal biomarkers cannot reliably exclude active inflammation in symptomatic patients 1
• The false negative rate is 24.7% in patients with moderate-to-severe symptoms and normal calprotectin 3
• Alternative: In patients preferring to avoid both endoscopy and treatment escalation, repeat biomarkers in 3-6 months 1

Asymptomatic/Symptomatic Remission + Calprotectin <150 μg/g

No intervention needed; this reliably rules out active inflammation. 1, 3

• In recently treated patients (within 1-3 months), consider the lower threshold of <50 μg/g to better detect endoscopic improvement 1
• Continue routine monitoring per treat-to-target protocols 1

Post-Surgical Crohn's Disease (Special Population)

For asymptomatic patients after intestinal resection:

• Low risk + on prophylaxis (10% recurrence prevalence): Calprotectin <150 μg/g rules out endoscopic recurrence with only 3.6% false negative rate 1
• High risk without prophylaxis (60% recurrence prevalence): Even calprotectin <50 μg/g has 4.2% false negative rate; consider endoscopy regardless 1
• Colonoscopic evaluation may be warranted beyond 12 months when using biomarker-based monitoring alone 1

Critical Pitfalls to Avoid

Non-IBD causes of elevation: Colorectal cancer, infectious gastroenteritis, NSAID use, and celiac disease all elevate calprotectin 3, 2. The standard >150 μg/g cutoff may be falsely positive in NSAID users, even at levels >250 μg/g 2.

Alarm symptoms override calprotectin: Rectal bleeding or significant abdominal pain requires cancer pathway referral regardless of calprotectin result, as it is not sensitive enough to exclude colorectal cancer 3.

Day-to-day variation: Borderline or unexpected results should prompt repeat testing before major clinical decisions 2, 4.

CRP limitations in UC: Normal CRP is less informative than fecal calprotectin for ruling out inflammation in ulcerative colitis patients, particularly in symptomatic remission 1.

Monitoring After Treatment Changes

• Repeat fecal calprotectin 2-4 months after initiating or adjusting therapy to assess response 5
• Consider endoscopic assessment 6-12 months after treatment initiation to confirm mucosal healing 5
• Serial monitoring at 3-6 month intervals facilitates early recognition of impending flares in known IBD 3