What is the management approach for elevated faecal (fecal) calprotectin levels in acute settings?

Management of Elevated Faecal Calprotectin in Acute Settings

In acute settings, elevated faecal calprotectin requires specific diagnostic pathways based on clinical presentation, as it cannot reliably differentiate between inflammatory bowel disease (IBD) and acute infectious gastroenteritis, necessitating stool culture and/or endoscopic evaluation for accurate diagnosis. 1

Interpretation of Elevated Faecal Calprotectin in Acute Presentations

• Faecal calprotectin is a calcium- and zinc-binding protein primarily derived from neutrophils, serving as a sensitive marker of intestinal inflammation 2
• In acute diarrhoea, calprotectin is likely to be elevated and will not discriminate between IBD and gastroenteritis, making stool culture and/or flexible sigmoidoscopy or colonoscopy the appropriate diagnostic investigations 1
• Calprotectin levels are significantly higher in bacterial infections (e.g., Salmonella, Campylobacter) compared to viral infections (rotavirus, norovirus, adenovirus) 3
• Elevated levels correlate with disease severity in infectious diarrhoea, with higher values seen in severe (median 843 μg/g) or moderate (median 402 μg/g) disease compared to mild disease (median 87 μg/g) 3

Diagnostic Approach in Acute Settings

• For patients with bloody diarrhoea, flexible sigmoidoscopy is indicated regardless of calprotectin result 1

• For patients with suspected acute infectious diarrhoea:

  • Obtain stool cultures to identify bacterial pathogens 1
  • Consider GI PCR panel testing alongside calprotectin measurement 4
  • Recognize that pathogen detection is associated with elevated calprotectin, though this relationship varies by IBD status 4

• For patients with rectal bleeding, abdominal pain, change in bowel habit, weight loss, or iron-deficiency anaemia:

  • Faecal calprotectin is not sensitive enough to exclude colorectal cancer 1
  • Cancer pathway referral should be strongly considered rather than relying on calprotectin 1

Management Based on Symptom Severity

Moderate to Severe Symptoms:

• In patients with moderate to severe symptoms suggestive of IBD flare (frequent rectal bleeding, significantly increased stool frequency):
  • Faecal calprotectin >150 μg/g can be used to rule in active inflammation and inform treatment adjustment without routine endoscopic assessment 1
  • However, normal calprotectin (<150 μg/g) does not reliably rule out inflammation in this setting 1

Mild Symptoms:

• For patients with mild symptoms (infrequent rectal bleeding and/or increased stool frequency):
  • Even with elevated calprotectin (>150 μg/g), endoscopic assessment is recommended rather than empiric treatment adjustment 1
  • Normal calprotectin (<150 μg/g) cannot reliably rule out active inflammation in this context 1

Follow-up Testing

• While evidence for routine repeat testing is limited, repeat measurement may be valuable 1
• In patients with initially elevated calprotectin (≥100 μg/g), repeat testing after approximately 18 days showed reduction in 53% of patients 1
• For patients in symptomatic remission but with persistently elevated biomarkers, repeat measurement in 3-6 months may be a reasonable alternative to immediate endoscopic assessment 1
• If biomarkers remain elevated on repeat evaluation, endoscopic assessment is warranted 1

Important Caveats and Limitations

• Practical issues with faecal calprotectin testing include:

  • Variability between different assays 1
  • Variability in levels from different stool samples from the same patient 1
  • Lack of stability for samples kept at room temperature for more than a few days 1
  • Variation related to the interval between stools being passed 1

• The appropriate cut-off for calprotectin should be determined locally but is generally between 100 and 250 μg/g stool 1

• Interpretation of calprotectin concentration must always consider the clinical history and symptoms specific to each patient 5

• Faecal calprotectin cannot substitute for stool pathogen testing in acute settings 4