What is the next step in managing a patient with a positive fecal calprotectin test and symptoms suggestive of inflammatory bowel disease (IBD)?

Management of Positive Fecal Calprotectin in Suspected IBD

Proceed directly to colonoscopy with ileoscopy and biopsies to confirm the diagnosis of IBD, assess disease extent and severity, and guide initial treatment decisions. 1, 2

Immediate Diagnostic Pathway

Endoscopic Evaluation

• Complete colonoscopy with terminal ileum intubation is the gold standard for diagnosing IBD and should be performed rather than flexible sigmoidoscopy alone to assess full disease extent 2
• Multiple biopsies must be obtained even from normal-appearing mucosa to establish histologic diagnosis 2
• The positive predictive value of fecal calprotectin for detecting endoscopically active disease is 78.2% at levels >100 μg/g 1

Pre-Endoscopy Laboratory Workup

Complete the following tests before or concurrent with gastroenterology referral 1:

• Complete blood count to assess for anemia and thrombocytosis (indicating inflammation) 1
• C-reactive protein (CRP) as a complementary inflammatory marker, though 20% of active Crohn's patients may have normal CRP 1
• Comprehensive metabolic panel including albumin (low albumin combined with elevated calprotectin improves positive predictive value for IBD) 1, 3
• Celiac screen (tissue transglutaminase antibodies) to exclude celiac disease 1
• Stool culture to exclude infectious causes of inflammation 1

Referral Urgency Based on Calprotectin Levels and Symptoms

For calprotectin >250 μg/g: Urgent gastroenterology referral is indicated regardless of symptom severity 1, 2

For calprotectin 100-250 μg/g with moderate-to-severe symptoms (rectal bleeding, significant abdominal pain, weight loss, frequent diarrhea): Urgent gastroenterology referral for colonoscopy 1

For calprotectin 100-250 μg/g with mild symptoms: Consider repeat calprotectin testing after 2-3 weeks or routine gastroenterology referral based on clinical suspicion 1

Critical Interpretation Considerations

Exclude Confounding Factors

• NSAID use within the past 6 weeks can falsely elevate calprotectin and warrants repeat testing after cessation 1, 4
• Hemorrhoids can cause false elevations due to local bleeding and inflammation 1
• Other conditions elevating calprotectin include infectious gastroenteritis, colorectal cancer, and microscopic colitis 1, 2

Alarm Features Requiring Cancer Pathway Referral

If any of the following are present, refer via suspected cancer pathway regardless of calprotectin level 1, 2:

• Rectal bleeding with abdominal pain
• Unexplained weight loss
• Iron-deficiency anemia
• Change in bowel habit in patients >40 years

Additional Imaging for Suspected Crohn's Disease

If Crohn's disease is suspected based on symptoms (right lower quadrant pain, perianal disease, oral ulcers), obtain MRI enterography or CT enterography to evaluate small bowel involvement and complications such as strictures, fistulas, or abscesses 1, 2

Common Pitfalls to Avoid

• Do not empirically adjust IBD treatment in patients with mild symptoms and elevated calprotectin without endoscopic confirmation of inflammation, as the false positive rate is 15.5% in this scenario 2
• Do not rely on calprotectin alone to exclude IBD—a normal calprotectin (<50 μg/g) has excellent negative predictive value, but 2-4% of IBD patients may have normal levels 1, 3
• Do not delay endoscopy for repeat calprotectin testing in patients with moderate-to-severe symptoms, as calprotectin >150 μg/g in this context has a 95.4% positive predictive value for moderate-to-severe endoscopic inflammation 2