In an adult or adolescent with chronic lower‑grade abdominal pain, diarrhea and weight loss, when should I order fecal calprotectin and how do I interpret its levels?

Fecal Calprotectin in Adults with Chronic Lower GI Symptoms

When to Order Fecal Calprotectin

Order fecal calprotectin in adults aged 16-40 presenting with chronic diarrhea, lower abdominal pain, and weight loss lasting more than 4 weeks when inflammatory bowel disease (IBD) is suspected and you need to differentiate it from irritable bowel syndrome (IBS). 1

Specific Clinical Scenarios for Testing:

• New-onset chronic lower GI symptoms (>4 weeks duration) including diarrhea, abdominal pain, and weight loss where IBD versus IBS is the diagnostic question 1, 2
• Exclude infectious causes first by obtaining stool culture (including C. difficile) before or concurrent with calprotectin testing 2, 3
• Document NSAID use in the past 6 weeks, as this can falsely elevate calprotectin and requires repeat testing after 6 weeks of cessation 2, 3

Critical Caveat - When NOT to Order:

Do not order fecal calprotectin if alarm features are present (rectal bleeding with abdominal pain, change in bowel habit, weight loss, iron-deficiency anemia, palpable mass, or unexplained anal ulceration) - these patients require immediate referral via a suspected cancer pathway regardless of calprotectin level, as calprotectin is not sensitive enough to exclude colorectal cancer. 1, 2, 3

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How to Interpret Fecal Calprotectin Levels

Collection Requirements:

• Use the first stool passed in the morning 1
• Store for no more than 3 days at room temperature before analysis 1
• Only one stool specimen is required for initial testing 2

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Interpretation Algorithm by Level:

Calprotectin <50 μg/g: IBD Effectively Ruled Out

• Excellent negative predictive value (90.6% sensitivity) for excluding IBD 1, 2
• Manage as functional bowel disorder (IBS) in primary care 2, 3
• If symptoms persist despite IBS treatment, consider alternative diagnoses: bile-acid malabsorption, microscopic colitis, or medication-induced symptoms 2

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Calprotectin 50-100 μg/g: Low Probability of IBD

• Treat as IBS in primary care if symptoms are consistent 2
• Consider repeat testing if clinical suspicion remains high 2

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Calprotectin 100-250 μg/g: Intermediate Range - Action Depends on Symptom Severity

This is the most challenging range to interpret, with moderate specificity (66%) at 100 μg/g. 1, 2

If Moderate-to-Severe Symptoms Present:

(Rectal bleeding, significant abdominal pain, weight loss >5%, frequent diarrhea >6 stools/day)

• Urgent gastroenterology referral within 1-2 weeks for colonoscopy 2, 3
• Complete baseline blood work before referral: complete blood count (assess anemia, thrombocytosis), C-reactive protein, comprehensive metabolic panel, celiac serology (tissue transglutaminase antibodies) 1, 2

If Mild or Minimal Symptoms:

• Repeat calprotectin testing in 2-3 weeks to determine if elevation is persistent or transient 2
• If repeat testing shows <100 μg/g and symptoms consistent with IBS, manage as functional disorder 2
• If repeat testing remains 100-250 μg/g or increases, proceed to routine gastroenterology referral (within 2-4 weeks) 2

If Strong Clinical Suspicion for IBD:

(Family history of IBD, young age, nocturnal symptoms, blood in stool)

• Direct gastroenterology referral without repeat testing 2

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Calprotectin >250 μg/g: High Probability of Active IBD

• Urgent gastroenterology referral within 1-2 weeks for colonoscopy regardless of symptom severity 1, 2, 3
• This threshold provides 82% specificity for differentiating active IBD from remission 1
• Complete baseline investigations: complete blood count, C-reactive protein, comprehensive metabolic panel, celiac serology, stool culture (including C. difficile) 2, 3

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Calprotectin >150 μg/g: Alternative Interpretation Framework

The American Gastroenterological Association uses 150 μg/g as a key threshold for clinical decision-making: 2, 4, 3

• In patients with moderate-to-severe symptoms: Only 4.6% false positive rate, meaning 95.4% have true moderate-to-severe endoscopic inflammation 2, 3
• In asymptomatic patients with known IBD: 22.4% false positive rate, suggesting endoscopic evaluation should be considered 3

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Non-IBD Causes of Elevated Calprotectin

Always consider alternative diagnoses when calprotectin is elevated: 1, 2, 3

• Infectious gastroenteritis (can markedly elevate levels) 2, 3
• Colorectal cancer (though calprotectin cannot reliably exclude this) 1, 2
• Microscopic colitis 2
• NSAID use within past 6 weeks 2, 3
• Hemorrhoids (local bleeding and inflammation) 2
• Celiac disease 3

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Endoscopic Evaluation When Indicated

Complete ileocolonoscopy with terminal ileum intubation is the gold standard when calprotectin warrants further investigation: 1, 2

• Obtain multiple biopsies from both affected and normal-appearing mucosa to document skip lesions and establish histologic diagnosis 1, 2
• Consider cross-sectional imaging (MRI or CT enterography) if Crohn's disease is suspected to assess small bowel involvement and complications (strictures, fistulas, abscesses) 1, 2

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Key Clinical Pearls

• Calprotectin correlates well with endoscopic inflammation in both ulcerative colitis and Crohn's disease, making it superior to C-reactive protein for detecting intestinal inflammation 1, 4
• Approximately 20% of patients with active Crohn's disease may have normal CRP, making calprotectin more sensitive 1
• Calprotectin has a positive likelihood ratio of 6.12 for detecting organic disease at cutoffs of 50-60 μg/g, compared to CRP's 3.4 2, 4
• Serial monitoring every 3-6 months in established IBD patients can facilitate early recognition of impending flares 2, 3