Should a patient with persistent gastrointestinal symptoms, such as abdominal pain, changes in bowel habits, or blood in the stool, undergo fecal calprotectin testing and colonoscopy?

Should a Patient with Persistent GI Symptoms Undergo Fecal Calprotectin Testing and Colonoscopy?

Yes, fecal calprotectin testing should be performed first in patients with persistent gastrointestinal symptoms (abdominal pain, changes in bowel habits, or blood in stool), with colonoscopy reserved for those with elevated calprotectin levels, alarm features, or age >50 years. 1

Initial Diagnostic Approach

Fecal Calprotectin Testing First

• Fecal calprotectin serves as an excellent screening tool to differentiate inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) in patients with lower gastrointestinal symptoms, with a high negative predictive value for ruling out IBD when levels are normal (<50 μg/g). 1

• The test has 90.6% sensitivity to detect endoscopically active disease at a cut-off of 50 μg/g, and 78.2% specificity at levels >100 μg/g. 1

• Overall diagnostic performance shows 78% sensitivity, 83% specificity, 86% positive predictive value, and 80% diagnostic efficacy for detecting organic disease. 2

Interpretation Algorithm Based on Calprotectin Levels

Calprotectin <100 μg/g:

• IBS is likely; manage in primary care without colonoscopy or gastroenterology referral. 1, 3
• Continue symptomatic management and reassurance. 4

Calprotectin 100-250 μg/g (Intermediate Range):

• Consider repeat testing after 2-3 weeks, as 53% of patients with initially elevated levels show reduction on repeat testing. 1, 5
• If persistently elevated or moderate-to-severe symptoms present, refer to gastroenterology for routine evaluation. 1, 3
• Complete baseline blood work (CBC, CRP, coeliac screen, stool culture) before referral. 1

Calprotectin >250 μg/g:

• Urgent gastroenterology referral for colonoscopy is indicated, as this strongly suggests active inflammatory disease. 1, 3
• Proceed directly to endoscopic evaluation. 1

Direct Indications for Colonoscopy (Regardless of Calprotectin)

Age-Based Screening

• Colonoscopy is recommended for all patients over age 50 years due to higher pretest probability of colon cancer, regardless of calprotectin level. 4

Alarm Features Requiring Immediate Colonoscopy

• Rectal bleeding with abdominal pain 1
• Unintentional weight loss 4
• Iron-deficiency anemia 1
• Change in bowel habits with blood in stool 1
• These patients should be referred via a suspected cancer pathway regardless of calprotectin level, as calprotectin is not sensitive enough to exclude colorectal cancer or advanced adenomas. 1, 5

Clinical Features Suggesting Organic Disease in Younger Patients

• Persistent diarrhea with weight loss 4
• Moderate-to-severe symptoms with calprotectin >150 μg/g 1, 3
• Family history of IBD or colorectal cancer 4

Essential Pre-Colonoscopy Testing

Before proceeding to colonoscopy or gastroenterology referral, complete the following baseline investigations: 1

• Complete blood count (assess for anemia, thrombocytosis indicating inflammation)
• C-reactive protein (complementary inflammatory marker, though 20% of active Crohn's patients may have normal CRP)
• Urea and electrolytes (assess for dehydration, electrolyte abnormalities)
• Coeliac screen (tissue transglutaminase antibodies to exclude celiac disease)
• Stool culture (exclude infectious causes of inflammation)
• Stool for ova and parasites if clinically indicated based on geographic area or travel history 4

Important Caveats and Pitfalls

Factors That Can Falsely Elevate Calprotectin

• NSAID use within the past 6 weeks can falsely elevate calprotectin levels; discontinue NSAIDs and repeat testing after cessation if documented use. 1, 5, 3, 6

• Hemorrhoids or other sources of gastrointestinal bleeding can elevate calprotectin without indicating IBD. 1, 5

• Infectious gastroenteritis will cause elevated calprotectin and cannot be distinguished from IBD by calprotectin alone; stool culture is essential. 1, 3

• Colorectal cancer and advanced adenomas can also cause elevated calprotectin. 1, 5

Proper Sample Collection

• The first stool passed in the morning should be used for sampling. 1, 5, 3

• Samples should be stored for no more than 3 days at room temperature before analysis. 1, 5

When Colonoscopy May Not Be Indicated

• Young patients (<50 years) with mild symptoms, normal calprotectin (<100 μg/g), no alarm features, and no family history of IBD or cancer can be managed conservatively with symptomatic treatment. 4

• For constipation-predominant symptoms without alarm features, a therapeutic trial of fiber may be sufficient initially. 4

• For diarrhea-predominant symptoms without alarm features and normal calprotectin, a therapeutic trial of loperamide can be ordered after excluding infection. 4

Special Considerations for Immune Checkpoint Inhibitor Patients

If the patient is receiving immune checkpoint inhibitor therapy, different thresholds apply: 4

• Grade 2 or higher diarrhea/colitis symptoms warrant immediate workup including fecal calprotectin, lactoferrin, and consideration for urgent colonoscopy with biopsy. 4

• Presence of ulceration on colonoscopy predicts steroid-refractory course requiring early infliximab. 4

• Fecal calprotectin level ≤116 mg/g can be considered the treatment target for documenting complete remission. 4